This article aims to study the effects of exogenous 24-epibrassinolide （EBR） on the changes in ROS, activities of antioxidative enzymes and antioxidants in cucumber （Cucumis sativus L.） seedling roots under hypoxi...This article aims to study the effects of exogenous 24-epibrassinolide （EBR） on the changes in ROS, activities of antioxidative enzymes and antioxidants in cucumber （Cucumis sativus L.） seedling roots under hypoxia stress. Seedlings of a hypoxiaresistant cultivar, Lühachun 4, and a hypoxia-sensitive cultivar, Zhongnong 8, were hydroponically grown for 8 d in normoxic or hypoxic nutrient solutions that were added or not added with 10^-3 mg L^-1 EBR. Under hypoxia stress, the ROS levels and the lipid peroxidation were significantly increased in the roots upon exposure to hypoxia stress, which were inhibited by EBR application. The EBR treatment significantly increased the seedlings growth and SOD, APX, GR activities, and contents of AsA and GSH under hypoxia stress. From the results obtained in this study, it can be concluded that oxidative damage on seedling roots by hypoxia stress can be considerably alleviated and the tolerance of plants was elevated.展开更多
In this thesis, 10 species of kiwifruit rootstocks were treated with hydroponics hypoxia to study their root zone hypoxia tolerance. The results were as follows: growth of all kiwifruit seedlings was inhibited. The ma...In this thesis, 10 species of kiwifruit rootstocks were treated with hydroponics hypoxia to study their root zone hypoxia tolerance. The results were as follows: growth of all kiwifruit seedlings was inhibited. The max length of new root, plant height, plant biomass, root activity, relative growth rate of leaves, and content of chlorophyll in leaves under root zone hypoxia stress obviously declined comparing with control. MDA content, relative conductance in the leaves and roots all increased in 10 kinds of kiwifruit seedlings. The sensitivities of 10 kinds’ kiwifruit seedlings to hypoxia stress were obviously different. With the method of subordinate function and cluster analysis, the adversity resistance coefficient of 10 kinds’ kiwifruit seedlings, were comprehensively evaluated in order to appraise their hypoxia-tolerance abilities. According to the results, “Hayward”, “Qinmei”, “Jinxiang”, “Kuoye”, “Huayou” kiwifruit seedlings held higher tolerance to root zone hypoxia stress, while “Hongyang” kiwifruit seedlings were sensitive to root zone hypoxia stress. The others, including “Xixuan”, “Maohua”, “Jinhua”, “Shanli” kiwifruit seedlings kept moderate resistant intensity to root zone hypoxia stress. The kiwifruit seedlings’ resistance order from strong to weak was: “Hayward” > “Qinmei” > “Jinxiang” > “Kuoye” > “Huayou” > “Xixuan” > “Maohua” > “Jinhua” > “Shanli” > “Hongyang”.展开更多
The changes of antioxidant enzyme activities and related genes expression of tomato seedlings were evaluated under hypoxia stress with different levels of Mn2+. Activities of superoxide dismutase (SOD), peroxidase (PO...The changes of antioxidant enzyme activities and related genes expression of tomato seedlings were evaluated under hypoxia stress with different levels of Mn2+. Activities of superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxide (APX), glutathione reductase (GR), catalase (CAT), the contents of H2O2, ascorbic (AsA) and malondialdehyde (MDA) were studied to investigate how active oxygen damaged the membrane lipid under hypoxia stress. With 10-200 μmol?L-1 Mn2+, the activities of SOD, POD, APX, GR and the contents of H2O2, AsA, MDA of leaves and roots increased significantly, which indicated that low Mn2+ could eliminate the active oxygen and protect the membrane lipid from hurt. But the activities of catalase (CAT) decreased evidently in the root. When the concentration of Mn2+ reached 400-600 μmol?L-1 under hypoxia stress, the activities of SOD, POD, APX, GR and ASA content decreased remarkably. However, the contents of H2O2 and MDA increased contrarily. A series of resistance genes level achieved peak value with 10 μmol?L-1 Mn2+. The expression level of SOD, CAT, APX, POD, GR were 6.28, 2.19, 5.66, 5.21 and 6.79 times compared to control respectively. These results illustrated appropriate amount of Mn2+ could reduce the damage of active oxygen under hypoxia stress, but reversely, high level of Mn2+ just aggravated the already serious damage to the tomato seedlings.展开更多
Background: Chronic fatigue syndrome (CFS) shows as its main symptoms debilitating fatigue that is not relieved by physiological rest, depression, inflammation, learning disability and memory impairment. But, intermit...Background: Chronic fatigue syndrome (CFS) shows as its main symptoms debilitating fatigue that is not relieved by physiological rest, depression, inflammation, learning disability and memory impairment. But, intermittent hypoxia, consisting of alternating exposure to hypoxia and normoxia, plays a very important role in improving CFS. However, the essential components for improving learning and memory in CFS patients as well as their mechanism are largely unknown. Objectives: This study aims to analyze the effects of 12% and 15% hypoxia on the expression of alpha tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB) in CFS induced-mouse model for clarifying the effects on the learning and memory function. Methods: A total of 48 type IC mice were used. The CFS mouse model was established using restrained stress and repeated forced swimming. Treatment of CFS was done by exposing CFS mice to intermittent hypoxia at 12% and 15%. The effects of intermittent hypoxia on learning and memory as well as its mechanism of action on inflammation were tested respectively with the Morris test, the SDS page, the immunohistochemistry technique and the Nissl staining. Results: We found that 12% and 15% intermittent hypoxia exposure improved learning capacity and memory of CFS induced-mice. SDS page showed that CFS caused higher TNF-α expression. By exposing CFS mice to 12% and 15% intermittent hypoxia, TNF-α expression decreased significantly, with a much better effect at 15%. Both TNF-α and NF-κB increased in CFS state and decreased after treatment with intermittent hypoxia. Conclusion: Intermittent hypoxia improves learning capacity and memory. It acted by decreasing NF-κB come to down-regulating TNF-α and ameliorates learning capacity and memory impairment in CFS mice.展开更多
The rapid elongation of rice(Oryza sativa)coleoptile is pivotal for the plant plumule to evade hypoxia stress induced by submergence,a condition often arising from overirrigation,ponding,rainstorms,or flooding.While b...The rapid elongation of rice(Oryza sativa)coleoptile is pivotal for the plant plumule to evade hypoxia stress induced by submergence,a condition often arising from overirrigation,ponding,rainstorms,or flooding.While brassinosteroids(BRs)are recognized for their diverse roles in plant growth and development,their influence on coleoptile elongation under hypoxic conditions remains largely unexplored.In this study,we demonstrate the significant requirement of BRs for coleoptile elongation in deep water.During coleoptile development,Glycogen Synthase Kinase3-Like Kinase2(GSK2),the central inhibitor of BR signaling in rice,undergoes substantial suppression in deep water but induction in air.In contrast,the dephosphorylated form of BRASSINAZOLE RESISTANT1(OsBZR1),representing the active form of the key BR signaling transcription factor,is induced in water but suppressed in air.Remarkably,the knockout of GSK3-like kinase genes significantly enhances coleoptile elongation in deep water,strongly indicating a vital contribution of BR response to hypoxia-stimulated coleoptile elongation.Transcriptome analysis uncovers both BR-associated and BR-independent hypoxia responses,implicating substance metabolism,redox reactions,abiotic stress responses,and crosstalk with other hormones in the regulation of BR-induced hypoxia responses.In summary,our findings suggest that rice plumules rapidly elongate coleoptiles through the activation of BR response in deep water,enabling them to escape from submergence-induced hypoxia stress.展开更多
Coronary heart disease (CHD) is a hypoxia related disease. However, the relationship of the hypoxia-induced oxidative stress, autophagy and apoptosis in cardiomyocyte remains unclear. In this study, we used CoCl2 to m...Coronary heart disease (CHD) is a hypoxia related disease. However, the relationship of the hypoxia-induced oxidative stress, autophagy and apoptosis in cardiomyocyte remains unclear. In this study, we used CoCl2 to mimic hypoxic conditions in H9c2 cardiomyocytes and study the effects of CoCl2-induced hypoxia on oxidative stress, apoptosis and autophagy, as well as the relationships among these processes. Cell viability and levels of ROS, LC3-II, p62, caspase-3 and PARP were assessed. The viability and morphology of cardiomyocytes were affected by hypoxia, and hypoxia enhanced levels of ROS and the levels of the LC3-II, p62, caspase-3 and PARP proteins in H9c2 cells in a dose-dependent manner. ROS levels rise gradually in the presence of hypoxia;however, it shrinks when hypoxia reaches a certain level. Caspase-3 and PARP levels were raised with the increasing of hypoxia level. Enhanced level of LC3 and decreased levels of p62 in hypoxic cells indicate that autophagy levels are in accord with hypoxia. Based on these results, hypoxia induces oxidative stress, apoptosis and autophagy in cardiomyocytes. Autophagy is a double-edged sword. At a low level, autophagy can resist oxidative stress and protect cardiomyocytes from oxidative stress, while high level autophagy can promote apoptosis of cardiomyocytes.展开更多
In the present study, retinal MOiler cells were cultured in vitro and treated with hydrogen peroxide （oxidative stressor） and cobalt chloride （hypoxic injury）. Following 24 hours of culture, compensatory hypertrop...In the present study, retinal MOiler cells were cultured in vitro and treated with hydrogen peroxide （oxidative stressor） and cobalt chloride （hypoxic injury）. Following 24 hours of culture, compensatory hypertrophy was observed and cellular apoptosis increased. Hypoxia enhanced the migration ability of retinal MOiler cells and induced the expression of a-smooth muscle actin. Oxidative stress altered the morphology of MOiler cells when compared with hypoxia treatment.展开更多
Rho kinase （ROCK） was the first downstream Rho effector found to mediate RhoA-induced actin cytoskeletal changes through effects on myosin light chain phosphorylation. There is abundant evidence that the ROCK pathwa...Rho kinase （ROCK） was the first downstream Rho effector found to mediate RhoA-induced actin cytoskeletal changes through effects on myosin light chain phosphorylation. There is abundant evidence that the ROCK pathway participates in the pathogenesis of retinal endothelial injury and proliferative epiretinal membrane traction. In this study, we investigated the effect of the ROCK pathway inhibitor Y-27632 on retinal Müller cells subjected to hypoxia or oxidative stress. Müller cells were subjected to hypoxia or oxidative stress by exposure to CoCl2 or H2O2. After a 24-hour treatment with Y-27632, the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide assay was used to assess the survival of Müller cells. Hoechst 33258 was used to detect apoptosis, while 2′,7′-dichlorodihydrofluorescein diacetate was used to measure reactive oxygen species generation. A transwell chamber system was used to examine the migration ability of Müller cells. Western blot assay was used to detect the expression levels of α-smooth muscle actin, glutamine synthetase and vimentin. After treatment with Y-27632, Müller cells subjected to hypoxia or oxidative stress exhibited a morphology similar to control cells. Y-27632 reduced apoptosis, α-smooth muscle actin expression and reactive oxygen species generation under oxidative stress, and it reduced cell migration under hypoxia. Y-27632 also upregulated glutamine synthetase expression under hypoxia but did not impact vimentin expression. These findings suggest that Y-27632 protects Müller cells against cellular injury caused by oxidative stress and hypoxia by inhibiting the ROCK pathway.展开更多
Background and Aim Adiponectin(APN) is a potent cardioprotective molecule.The present study aims to investigate the under-lying mechanism(s) for its cardioprotective effect.Methods Primary cardiomyocytes were isolated...Background and Aim Adiponectin(APN) is a potent cardioprotective molecule.The present study aims to investigate the under-lying mechanism(s) for its cardioprotective effect.Methods Primary cardiomyocytes were isolated from neonatal rats and an invitro model of hypoxia-reoxygenation(H/R) was established.The cardiomyocytes were randomly divided into six groups: salinegroup(control),dithiothreitol(DTT) group(5 mmol/L DTTfor 2 h),H/R group,H/R +APN group(incubation with 30 mg/LAPN,followed by H/R),H/R +APN +SB203580(SB) group(treatment with 30 mg/L APN and 5μmol/L SB,followed by H/R),and H/R +SB group(exposure to 5μmol/L SB and then H/R).Cell death was detected by measuring lactate dehydrogenase(LDH) release.The expression levels of hypoxia-inducible factor-1alpha(HIF-1α) and endoplasmic reticulum(ER) stress-relatedgenes including GRP78,caspase-12,C/EBP homologus protein(CHOP),and p38 mitogen-activated protein kinase(MAPK) wereexamined.Results Cardiomyocytes exposed to H/R showed a significant increase in LDH leakage and HIF-1αprotein levelscompared with the control cells(P<0.05).The H/R-provoked cell death was profoundly attenuated by the pretreatment with APNalone,SB alone,or both,which was coupled with decreased expression of GRP78,caspase-12,CHOP,and p38 MAPK.Conclu-sions These results provide new insights into the mechanism of APN-mediated cardioprotection,which may be partially due to inhibi-tion of ER stress response.展开更多
AIM:To study the effect of both acute and chronic alcohol exposure on heme oxygenases(HOs) in the brain,liver and duodenum.METHODS:Wild-type C57BL/6 mice,heterozygous Sod2 knockout mice,which exhibit attenuated mangan...AIM:To study the effect of both acute and chronic alcohol exposure on heme oxygenases(HOs) in the brain,liver and duodenum.METHODS:Wild-type C57BL/6 mice,heterozygous Sod2 knockout mice,which exhibit attenuated manganese superoxide dismutase activity,and liver-specific ARNT knockout mice were used to investigate the role of alcohol-induced oxidative stress and hypoxia.For acute alcohol exposure,ethanol was administered in the drinking water for 1 wk.Mice were pair-fed with regular or ethanol-containing Lieber De Carli liquid diets for 4 wk for chronic alcohol studies.HO expression was analyzed by real-time quantitative polymerase chain reaction and Western blotting.RESULTS:Chronic alcohol exposure downregulated HO-1 expression in the brain but upregulated it in the duodenum of wild-type mice.It did not alter liver HO-1 expression,nor HO-2 expression in the brain,liver or duodenum.In contrast,acute alcohol exposure decreased both liver HO-1 and HO-2 expression,and HO-2 expression in the duodenum of wild-type mice.The decrease in liver HO-1 expression was abolished in ARNT+/-mice.Sod2+/-mice with acute alcohol exposure did not exhibit any changes in liver HO-1 and HO-2 expression or in brain HO-2 expression.However,alcohol inhibited brain HO-1 and duodenal HO-2 but increased duodenal HO-1 expression in Sod2+/-mice.Collectively,these findings indicate that acute and chronic alcohol exposure regulates HO expression in a tissue-specific manner.Chronic alcohol exposure alters brain and duodenal,but not liver HO expression.However,acute alcohol exposure inhibits liver HO-1 and HO-2,and also duodenal HO-2 expression.CONCLUSION:The inhibition of liver HO expression by acute alcohol-induced hypoxia may play a role in the early phases of alcoholic liver disease progression.展开更多
This study cloned the hemoglobin a1 from the marine teleost, the half-smooth tongue sole （Cynoglossus semilaevis）, and then examined its expression under hypoxia exposure. The full-length of CsHb-a1 （594 bp） cDNA ...This study cloned the hemoglobin a1 from the marine teleost, the half-smooth tongue sole （Cynoglossus semilaevis）, and then examined its expression under hypoxia exposure. The full-length of CsHb-a1 （594 bp） cDNA contains an open reading frame encoding 144 amino acids. Sequence analysis shows that the predicted CsHb-a1 amino acids shares high identities with that of other species. Real-time PCR showed that CsHb-a1 was highly expressed in the heart, liver, spleen, kidney and blood. Five to 120 min esposure and long-term （36 h） exposure to hypoxia （1.0 mg/L） significantly increased CsHb-a1 mRNA expression in most tissues compared to those fish held in normoxic conditions （dissolved oxygen （DO）： 6.2 mg/L）. These results suggested that the up-regulation of Hb-a1 is an important component for adaptation of half-smooth tongue sole to short-term hypoxia.展开更多
Using a rat oxidative stress-induced femoral head osteonecrosis model, we determined the presence/ absence and timing of the generation of hypoxia in the femoral head. DL-Buthionine-(S,R)-sulfoximine (BSO) 500 mg/kg w...Using a rat oxidative stress-induced femoral head osteonecrosis model, we determined the presence/ absence and timing of the generation of hypoxia in the femoral head. DL-Buthionine-(S,R)-sulfoximine (BSO) 500 mg/kg was administered intraperitoneally to male Wistar rats. The rats were killed at 1, 3, 6, 12 hours, and 1, 3, 5 days after BSO administration, and the bilateral femora were removed. A group not administered BSO (control group) was also studied (each group n = 5). In the femoral heads of each group, the expression of hypoxia-inducible factor-1 alpha (HIF-1α) as an index of hypoxia was confirmed by the Western blot method, and quantified using analytical software. In the femoral head increased HIF-1α expression was found in all groups from 1 hour after BSO administration (p < 0.05). In particular, in all specimens of the group 3 hours after BSO administration the most intense expression of HIF-1α amounting to about 13-fold of that of control group was noted (p < 0.001). The present results suggested that in the extremely short period of 3 hours after BSO administration hypoxia severe enough to cause osteonecrosis was induced by oxidative stress in the rat femoral head.展开更多
文摘This article aims to study the effects of exogenous 24-epibrassinolide （EBR） on the changes in ROS, activities of antioxidative enzymes and antioxidants in cucumber （Cucumis sativus L.） seedling roots under hypoxia stress. Seedlings of a hypoxiaresistant cultivar, Lühachun 4, and a hypoxia-sensitive cultivar, Zhongnong 8, were hydroponically grown for 8 d in normoxic or hypoxic nutrient solutions that were added or not added with 10^-3 mg L^-1 EBR. Under hypoxia stress, the ROS levels and the lipid peroxidation were significantly increased in the roots upon exposure to hypoxia stress, which were inhibited by EBR application. The EBR treatment significantly increased the seedlings growth and SOD, APX, GR activities, and contents of AsA and GSH under hypoxia stress. From the results obtained in this study, it can be concluded that oxidative damage on seedling roots by hypoxia stress can be considerably alleviated and the tolerance of plants was elevated.
文摘In this thesis, 10 species of kiwifruit rootstocks were treated with hydroponics hypoxia to study their root zone hypoxia tolerance. The results were as follows: growth of all kiwifruit seedlings was inhibited. The max length of new root, plant height, plant biomass, root activity, relative growth rate of leaves, and content of chlorophyll in leaves under root zone hypoxia stress obviously declined comparing with control. MDA content, relative conductance in the leaves and roots all increased in 10 kinds of kiwifruit seedlings. The sensitivities of 10 kinds’ kiwifruit seedlings to hypoxia stress were obviously different. With the method of subordinate function and cluster analysis, the adversity resistance coefficient of 10 kinds’ kiwifruit seedlings, were comprehensively evaluated in order to appraise their hypoxia-tolerance abilities. According to the results, “Hayward”, “Qinmei”, “Jinxiang”, “Kuoye”, “Huayou” kiwifruit seedlings held higher tolerance to root zone hypoxia stress, while “Hongyang” kiwifruit seedlings were sensitive to root zone hypoxia stress. The others, including “Xixuan”, “Maohua”, “Jinhua”, “Shanli” kiwifruit seedlings kept moderate resistant intensity to root zone hypoxia stress. The kiwifruit seedlings’ resistance order from strong to weak was: “Hayward” > “Qinmei” > “Jinxiang” > “Kuoye” > “Huayou” > “Xixuan” > “Maohua” > “Jinhua” > “Shanli” > “Hongyang”.
文摘The changes of antioxidant enzyme activities and related genes expression of tomato seedlings were evaluated under hypoxia stress with different levels of Mn2+. Activities of superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxide (APX), glutathione reductase (GR), catalase (CAT), the contents of H2O2, ascorbic (AsA) and malondialdehyde (MDA) were studied to investigate how active oxygen damaged the membrane lipid under hypoxia stress. With 10-200 μmol?L-1 Mn2+, the activities of SOD, POD, APX, GR and the contents of H2O2, AsA, MDA of leaves and roots increased significantly, which indicated that low Mn2+ could eliminate the active oxygen and protect the membrane lipid from hurt. But the activities of catalase (CAT) decreased evidently in the root. When the concentration of Mn2+ reached 400-600 μmol?L-1 under hypoxia stress, the activities of SOD, POD, APX, GR and ASA content decreased remarkably. However, the contents of H2O2 and MDA increased contrarily. A series of resistance genes level achieved peak value with 10 μmol?L-1 Mn2+. The expression level of SOD, CAT, APX, POD, GR were 6.28, 2.19, 5.66, 5.21 and 6.79 times compared to control respectively. These results illustrated appropriate amount of Mn2+ could reduce the damage of active oxygen under hypoxia stress, but reversely, high level of Mn2+ just aggravated the already serious damage to the tomato seedlings.
文摘Background: Chronic fatigue syndrome (CFS) shows as its main symptoms debilitating fatigue that is not relieved by physiological rest, depression, inflammation, learning disability and memory impairment. But, intermittent hypoxia, consisting of alternating exposure to hypoxia and normoxia, plays a very important role in improving CFS. However, the essential components for improving learning and memory in CFS patients as well as their mechanism are largely unknown. Objectives: This study aims to analyze the effects of 12% and 15% hypoxia on the expression of alpha tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB) in CFS induced-mouse model for clarifying the effects on the learning and memory function. Methods: A total of 48 type IC mice were used. The CFS mouse model was established using restrained stress and repeated forced swimming. Treatment of CFS was done by exposing CFS mice to intermittent hypoxia at 12% and 15%. The effects of intermittent hypoxia on learning and memory as well as its mechanism of action on inflammation were tested respectively with the Morris test, the SDS page, the immunohistochemistry technique and the Nissl staining. Results: We found that 12% and 15% intermittent hypoxia exposure improved learning capacity and memory of CFS induced-mice. SDS page showed that CFS caused higher TNF-α expression. By exposing CFS mice to 12% and 15% intermittent hypoxia, TNF-α expression decreased significantly, with a much better effect at 15%. Both TNF-α and NF-κB increased in CFS state and decreased after treatment with intermittent hypoxia. Conclusion: Intermittent hypoxia improves learning capacity and memory. It acted by decreasing NF-κB come to down-regulating TNF-α and ameliorates learning capacity and memory impairment in CFS mice.
基金supported by STI 2030–Major Projects (2023ZD0407101)National Key Research and Development Program of China (2022YFD1201700)+1 种基金National Natural Science Foundation (U21A20208,32201704)Innovation Program of CAAS。
文摘The rapid elongation of rice(Oryza sativa)coleoptile is pivotal for the plant plumule to evade hypoxia stress induced by submergence,a condition often arising from overirrigation,ponding,rainstorms,or flooding.While brassinosteroids(BRs)are recognized for their diverse roles in plant growth and development,their influence on coleoptile elongation under hypoxic conditions remains largely unexplored.In this study,we demonstrate the significant requirement of BRs for coleoptile elongation in deep water.During coleoptile development,Glycogen Synthase Kinase3-Like Kinase2(GSK2),the central inhibitor of BR signaling in rice,undergoes substantial suppression in deep water but induction in air.In contrast,the dephosphorylated form of BRASSINAZOLE RESISTANT1(OsBZR1),representing the active form of the key BR signaling transcription factor,is induced in water but suppressed in air.Remarkably,the knockout of GSK3-like kinase genes significantly enhances coleoptile elongation in deep water,strongly indicating a vital contribution of BR response to hypoxia-stimulated coleoptile elongation.Transcriptome analysis uncovers both BR-associated and BR-independent hypoxia responses,implicating substance metabolism,redox reactions,abiotic stress responses,and crosstalk with other hormones in the regulation of BR-induced hypoxia responses.In summary,our findings suggest that rice plumules rapidly elongate coleoptiles through the activation of BR response in deep water,enabling them to escape from submergence-induced hypoxia stress.
文摘Coronary heart disease (CHD) is a hypoxia related disease. However, the relationship of the hypoxia-induced oxidative stress, autophagy and apoptosis in cardiomyocyte remains unclear. In this study, we used CoCl2 to mimic hypoxic conditions in H9c2 cardiomyocytes and study the effects of CoCl2-induced hypoxia on oxidative stress, apoptosis and autophagy, as well as the relationships among these processes. Cell viability and levels of ROS, LC3-II, p62, caspase-3 and PARP were assessed. The viability and morphology of cardiomyocytes were affected by hypoxia, and hypoxia enhanced levels of ROS and the levels of the LC3-II, p62, caspase-3 and PARP proteins in H9c2 cells in a dose-dependent manner. ROS levels rise gradually in the presence of hypoxia;however, it shrinks when hypoxia reaches a certain level. Caspase-3 and PARP levels were raised with the increasing of hypoxia level. Enhanced level of LC3 and decreased levels of p62 in hypoxic cells indicate that autophagy levels are in accord with hypoxia. Based on these results, hypoxia induces oxidative stress, apoptosis and autophagy in cardiomyocytes. Autophagy is a double-edged sword. At a low level, autophagy can resist oxidative stress and protect cardiomyocytes from oxidative stress, while high level autophagy can promote apoptosis of cardiomyocytes.
文摘In the present study, retinal MOiler cells were cultured in vitro and treated with hydrogen peroxide （oxidative stressor） and cobalt chloride （hypoxic injury）. Following 24 hours of culture, compensatory hypertrophy was observed and cellular apoptosis increased. Hypoxia enhanced the migration ability of retinal MOiler cells and induced the expression of a-smooth muscle actin. Oxidative stress altered the morphology of MOiler cells when compared with hypoxia treatment.
基金financially supported by the Scientific and Technological Project of Shaanxi Province of China,No.2016SF-010
文摘Rho kinase （ROCK） was the first downstream Rho effector found to mediate RhoA-induced actin cytoskeletal changes through effects on myosin light chain phosphorylation. There is abundant evidence that the ROCK pathway participates in the pathogenesis of retinal endothelial injury and proliferative epiretinal membrane traction. In this study, we investigated the effect of the ROCK pathway inhibitor Y-27632 on retinal Müller cells subjected to hypoxia or oxidative stress. Müller cells were subjected to hypoxia or oxidative stress by exposure to CoCl2 or H2O2. After a 24-hour treatment with Y-27632, the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide assay was used to assess the survival of Müller cells. Hoechst 33258 was used to detect apoptosis, while 2′,7′-dichlorodihydrofluorescein diacetate was used to measure reactive oxygen species generation. A transwell chamber system was used to examine the migration ability of Müller cells. Western blot assay was used to detect the expression levels of α-smooth muscle actin, glutamine synthetase and vimentin. After treatment with Y-27632, Müller cells subjected to hypoxia or oxidative stress exhibited a morphology similar to control cells. Y-27632 reduced apoptosis, α-smooth muscle actin expression and reactive oxygen species generation under oxidative stress, and it reduced cell migration under hypoxia. Y-27632 also upregulated glutamine synthetase expression under hypoxia but did not impact vimentin expression. These findings suggest that Y-27632 protects Müller cells against cellular injury caused by oxidative stress and hypoxia by inhibiting the ROCK pathway.
文摘Background and Aim Adiponectin(APN) is a potent cardioprotective molecule.The present study aims to investigate the under-lying mechanism(s) for its cardioprotective effect.Methods Primary cardiomyocytes were isolated from neonatal rats and an invitro model of hypoxia-reoxygenation(H/R) was established.The cardiomyocytes were randomly divided into six groups: salinegroup(control),dithiothreitol(DTT) group(5 mmol/L DTTfor 2 h),H/R group,H/R +APN group(incubation with 30 mg/LAPN,followed by H/R),H/R +APN +SB203580(SB) group(treatment with 30 mg/L APN and 5μmol/L SB,followed by H/R),and H/R +SB group(exposure to 5μmol/L SB and then H/R).Cell death was detected by measuring lactate dehydrogenase(LDH) release.The expression levels of hypoxia-inducible factor-1alpha(HIF-1α) and endoplasmic reticulum(ER) stress-relatedgenes including GRP78,caspase-12,C/EBP homologus protein(CHOP),and p38 mitogen-activated protein kinase(MAPK) wereexamined.Results Cardiomyocytes exposed to H/R showed a significant increase in LDH leakage and HIF-1αprotein levelscompared with the control cells(P<0.05).The H/R-provoked cell death was profoundly attenuated by the pretreatment with APNalone,SB alone,or both,which was coupled with decreased expression of GRP78,caspase-12,CHOP,and p38 MAPK.Conclu-sions These results provide new insights into the mechanism of APN-mediated cardioprotection,which may be partially due to inhibi-tion of ER stress response.
基金Supported by University of Nebraska Medical Center Funds and NIH grant (R01AA017738) to Harrison-Findik DD
文摘AIM:To study the effect of both acute and chronic alcohol exposure on heme oxygenases(HOs) in the brain,liver and duodenum.METHODS:Wild-type C57BL/6 mice,heterozygous Sod2 knockout mice,which exhibit attenuated manganese superoxide dismutase activity,and liver-specific ARNT knockout mice were used to investigate the role of alcohol-induced oxidative stress and hypoxia.For acute alcohol exposure,ethanol was administered in the drinking water for 1 wk.Mice were pair-fed with regular or ethanol-containing Lieber De Carli liquid diets for 4 wk for chronic alcohol studies.HO expression was analyzed by real-time quantitative polymerase chain reaction and Western blotting.RESULTS:Chronic alcohol exposure downregulated HO-1 expression in the brain but upregulated it in the duodenum of wild-type mice.It did not alter liver HO-1 expression,nor HO-2 expression in the brain,liver or duodenum.In contrast,acute alcohol exposure decreased both liver HO-1 and HO-2 expression,and HO-2 expression in the duodenum of wild-type mice.The decrease in liver HO-1 expression was abolished in ARNT+/-mice.Sod2+/-mice with acute alcohol exposure did not exhibit any changes in liver HO-1 and HO-2 expression or in brain HO-2 expression.However,alcohol inhibited brain HO-1 and duodenal HO-2 but increased duodenal HO-1 expression in Sod2+/-mice.Collectively,these findings indicate that acute and chronic alcohol exposure regulates HO expression in a tissue-specific manner.Chronic alcohol exposure alters brain and duodenal,but not liver HO expression.However,acute alcohol exposure inhibits liver HO-1 and HO-2,and also duodenal HO-2 expression.CONCLUSION:The inhibition of liver HO expression by acute alcohol-induced hypoxia may play a role in the early phases of alcoholic liver disease progression.
基金supported by Nature Science Foundation of Jiangsu Province(BK2011418)the Graduate Research and Innovation of Colleges and Universities in Jiangsu Province(CX09B_106Z)Natural Science Foundation of the Jiangsu Higher Education Institutions of China(09KJD240004)
文摘This study cloned the hemoglobin a1 from the marine teleost, the half-smooth tongue sole （Cynoglossus semilaevis）, and then examined its expression under hypoxia exposure. The full-length of CsHb-a1 （594 bp） cDNA contains an open reading frame encoding 144 amino acids. Sequence analysis shows that the predicted CsHb-a1 amino acids shares high identities with that of other species. Real-time PCR showed that CsHb-a1 was highly expressed in the heart, liver, spleen, kidney and blood. Five to 120 min esposure and long-term （36 h） exposure to hypoxia （1.0 mg/L） significantly increased CsHb-a1 mRNA expression in most tissues compared to those fish held in normoxic conditions （dissolved oxygen （DO）： 6.2 mg/L）. These results suggested that the up-regulation of Hb-a1 is an important component for adaptation of half-smooth tongue sole to short-term hypoxia.
文摘Using a rat oxidative stress-induced femoral head osteonecrosis model, we determined the presence/ absence and timing of the generation of hypoxia in the femoral head. DL-Buthionine-(S,R)-sulfoximine (BSO) 500 mg/kg was administered intraperitoneally to male Wistar rats. The rats were killed at 1, 3, 6, 12 hours, and 1, 3, 5 days after BSO administration, and the bilateral femora were removed. A group not administered BSO (control group) was also studied (each group n = 5). In the femoral heads of each group, the expression of hypoxia-inducible factor-1 alpha (HIF-1α) as an index of hypoxia was confirmed by the Western blot method, and quantified using analytical software. In the femoral head increased HIF-1α expression was found in all groups from 1 hour after BSO administration (p < 0.05). In particular, in all specimens of the group 3 hours after BSO administration the most intense expression of HIF-1α amounting to about 13-fold of that of control group was noted (p < 0.001). The present results suggested that in the extremely short period of 3 hours after BSO administration hypoxia severe enough to cause osteonecrosis was induced by oxidative stress in the rat femoral head.
