The effects of steroid hormones are believed to be mediated by their nuclear receptors(NRs).The p160 coactivator family,including steroid receptor coactivator-1(SRC-1),2 and 3,has been shown to physically interact wit...The effects of steroid hormones are believed to be mediated by their nuclear receptors(NRs).The p160 coactivator family,including steroid receptor coactivator-1(SRC-1),2 and 3,has been shown to physically interact with NRs to enhance their transactivational activities.Among which SRC-1 has been predominantly localized in the central nervous system including brain and spinal cord.It is not only localized in neurons but also detectable in neuroglial cells(mainly localized in the nuclei but also detectable in the extra-nuclear components).Although the expression of SRC-1 is regulated by many steroids,it is also regulated by some non-steroidal factors such as injury,sound and light.Functionally,SRC-1 has been implied in normal function such as development and ageing,learning and memory,central regulation on reproductive behaviors,motor and food intake.Pathologically,SRC-1 may play a role in the regulation of neuropsychiatric disorders(including stress,depression,anxiety,and autism spectrum disorder),metabolite homeostasis and obesity as well as tumorigenesis.Under most conditions,the related mechanisms are far from elucidation;although it may regulate spatial memory through Rictor/mTORC2-actin polymerization related synaptic plasticity.Several inhibitors and stimulator of SRC-1 have shown anti-cancer potentials,but whether these small molecules could be used to modulate ageing and central disorder related neuropathology remain unclear.Therefore,to elucidate when and how SRC-1 is turned on and off under different stimuli is very interesting and great challenge for neuroscientists.展开更多
Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes m...Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes mellitus(GDM).Methods:A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM.A total of 21 pregnant rats with GDM were randomly divided into three groups,with 7ruts in each group,namely the insulin group,metformin group and control group.Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day.Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day,with the first dose of 300 mg/kg.The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L.Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day.After the natural delivery of pregnant rats.10 offspring rats were randomly selected from each group.At birth,4 wk and 8 wk after the birth of offspring rats,the weight of offspring rats was measured.The blood glucose level of offspring rats was measured at 4wk and 8 wk,while the level of serum insulin,triglyceride and leptin was measured at 8 wk.Results:The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group(P<0.05),and there was no significant difference at 4 wk and 8 wk among three groups(P>0.05).The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group(P<0.05);there was no significant difference between the insulin group and metformin group(P>0.05).The expression of PPARGC1 A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1 A was significantly lower than the one in the control group(P<0.05),but there was no significant difference between the insulin group and metformin group(P>0.05).Insulin and leptin at 8 wk in the insulin group and metformin group were significantly higher,while triglyceride was significantly lower than the one in the control group(P<0.05);triglyceride level of rats in the insulin group was significantly higher than the one in the metformin group(P<0.05).There was no significant difference in insulin and leptin level of offspring rats between the insulin group and metformin group(P>0.05).Conclusions:GDM can induce the methylation of PPARGC1 A of offspring rats to reduce the expression of PPARGC1 A mRNA and then cause the disorder of glycolipid metabolism when the offspring rats grow up;the insulin or metformin in the treatment of pregnant rats with GDM can reduce the methylation level of PPARGC1 A and thus improve the abnormal glycolipid metabolism of offspring rats.展开更多
Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via a...Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via an animal model, whether the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and the amino peptide neuropeptide Y (NPY) play a role in the pathogenesis of this cardiac entity. Male Sprague-Dawley rats in the experimental group were subjected to immobilization in a plexy glass box for 1 h, which was followed by low voltage elec-tric foot shock for about 1h at 10s intervals in a cage fitted with metallic rods. After 25 days the rats were sacrificed and sections of their hearts were processed. Hematoxylin-eosin staining of cardiac tissues revealed the characteristic cardiac lesions of stress cardiomyopathy such as contraction band necrosis, inflammatory cell infiltration and fibrosis. The semi-quantitative RT-PCR analysis for PGC-1α mRNA expression showed significant overexpression of PGC1-α in the stress-subjected rats (P<0.05). Fluorescence immunohistochemistry revealed a higher production of NPY in the stress-subjected rats as compared to the control rats (P=0.0027). Thus, we are led to conclude that following periods of intense stress, an increased expression of PGC1-α in the heart and an overflow of NPY may lead to stress car-diomyopathy and even death in susceptible victims. Moreover, these markers can be used to identify stress cardiomyopathy as the cause of sudden death in specific cases.展开更多
Hormone replacement therapy is necessary for patients with adrenal and gonadal failure.Steroid hormone treatment is also employed in aging people for sex hormone deficiency.These patients undergo such therapies,which ...Hormone replacement therapy is necessary for patients with adrenal and gonadal failure.Steroid hormone treatment is also employed in aging people for sex hormone deficiency.These patients undergo such therapies,which have associated risks,for their entire life.Stem cells represent an innovative tool for tissue regeneration and the possibility of solving these problems.Among various stem cell types,mesenchymal stem cells have the potential to differentiate into steroidogenic cells both in vivo and in vitro.In particular,they can effectively be differentiated into steroidogenic cells by expressing nuclear receptor 5A subfamily proteins(steroidogenic factor-1 and liver receptor homolog-1)with the aid of cAMP.This approach will provide a source of cells for future regenerative medicine for the treatment of diseases caused by steroidogenesis deficiencies.It can also represent a useful tool for studying the molecular mechanisms of steroidogenesis and its related diseases.展开更多
基金supported by the National Science Foundation of China(NSFC,No.81571059)the Postdoctoral Research Foundation of China(No.2019M653976)Natural Science Foundation of Chongqing,China(No.cstc2019jcyj-msxmX0255).
文摘The effects of steroid hormones are believed to be mediated by their nuclear receptors(NRs).The p160 coactivator family,including steroid receptor coactivator-1(SRC-1),2 and 3,has been shown to physically interact with NRs to enhance their transactivational activities.Among which SRC-1 has been predominantly localized in the central nervous system including brain and spinal cord.It is not only localized in neurons but also detectable in neuroglial cells(mainly localized in the nuclei but also detectable in the extra-nuclear components).Although the expression of SRC-1 is regulated by many steroids,it is also regulated by some non-steroidal factors such as injury,sound and light.Functionally,SRC-1 has been implied in normal function such as development and ageing,learning and memory,central regulation on reproductive behaviors,motor and food intake.Pathologically,SRC-1 may play a role in the regulation of neuropsychiatric disorders(including stress,depression,anxiety,and autism spectrum disorder),metabolite homeostasis and obesity as well as tumorigenesis.Under most conditions,the related mechanisms are far from elucidation;although it may regulate spatial memory through Rictor/mTORC2-actin polymerization related synaptic plasticity.Several inhibitors and stimulator of SRC-1 have shown anti-cancer potentials,but whether these small molecules could be used to modulate ageing and central disorder related neuropathology remain unclear.Therefore,to elucidate when and how SRC-1 is turned on and off under different stimuli is very interesting and great challenge for neuroscientists.
基金supported by Shandong Natural Science Fund(Y2008c170)
文摘Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes mellitus(GDM).Methods:A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM.A total of 21 pregnant rats with GDM were randomly divided into three groups,with 7ruts in each group,namely the insulin group,metformin group and control group.Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day.Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day,with the first dose of 300 mg/kg.The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L.Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day.After the natural delivery of pregnant rats.10 offspring rats were randomly selected from each group.At birth,4 wk and 8 wk after the birth of offspring rats,the weight of offspring rats was measured.The blood glucose level of offspring rats was measured at 4wk and 8 wk,while the level of serum insulin,triglyceride and leptin was measured at 8 wk.Results:The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group(P<0.05),and there was no significant difference at 4 wk and 8 wk among three groups(P>0.05).The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group(P<0.05);there was no significant difference between the insulin group and metformin group(P>0.05).The expression of PPARGC1 A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1 A was significantly lower than the one in the control group(P<0.05),but there was no significant difference between the insulin group and metformin group(P>0.05).Insulin and leptin at 8 wk in the insulin group and metformin group were significantly higher,while triglyceride was significantly lower than the one in the control group(P<0.05);triglyceride level of rats in the insulin group was significantly higher than the one in the metformin group(P<0.05).There was no significant difference in insulin and leptin level of offspring rats between the insulin group and metformin group(P>0.05).Conclusions:GDM can induce the methylation of PPARGC1 A of offspring rats to reduce the expression of PPARGC1 A mRNA and then cause the disorder of glycolipid metabolism when the offspring rats grow up;the insulin or metformin in the treatment of pregnant rats with GDM can reduce the methylation level of PPARGC1 A and thus improve the abnormal glycolipid metabolism of offspring rats.
基金supported by a grant from the National Natural Science Foundation of China(No.81172898)
文摘Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via an animal model, whether the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and the amino peptide neuropeptide Y (NPY) play a role in the pathogenesis of this cardiac entity. Male Sprague-Dawley rats in the experimental group were subjected to immobilization in a plexy glass box for 1 h, which was followed by low voltage elec-tric foot shock for about 1h at 10s intervals in a cage fitted with metallic rods. After 25 days the rats were sacrificed and sections of their hearts were processed. Hematoxylin-eosin staining of cardiac tissues revealed the characteristic cardiac lesions of stress cardiomyopathy such as contraction band necrosis, inflammatory cell infiltration and fibrosis. The semi-quantitative RT-PCR analysis for PGC-1α mRNA expression showed significant overexpression of PGC1-α in the stress-subjected rats (P<0.05). Fluorescence immunohistochemistry revealed a higher production of NPY in the stress-subjected rats as compared to the control rats (P=0.0027). Thus, we are led to conclude that following periods of intense stress, an increased expression of PGC1-α in the heart and an overflow of NPY may lead to stress car-diomyopathy and even death in susceptible victims. Moreover, these markers can be used to identify stress cardiomyopathy as the cause of sudden death in specific cases.
基金Supported by Ministry of Education,Culture,Sports,Science and Technology of Japan,No.23590329the Terumo Life Science Foundationthe Smoking Research Foundation
文摘Hormone replacement therapy is necessary for patients with adrenal and gonadal failure.Steroid hormone treatment is also employed in aging people for sex hormone deficiency.These patients undergo such therapies,which have associated risks,for their entire life.Stem cells represent an innovative tool for tissue regeneration and the possibility of solving these problems.Among various stem cell types,mesenchymal stem cells have the potential to differentiate into steroidogenic cells both in vivo and in vitro.In particular,they can effectively be differentiated into steroidogenic cells by expressing nuclear receptor 5A subfamily proteins(steroidogenic factor-1 and liver receptor homolog-1)with the aid of cAMP.This approach will provide a source of cells for future regenerative medicine for the treatment of diseases caused by steroidogenesis deficiencies.It can also represent a useful tool for studying the molecular mechanisms of steroidogenesis and its related diseases.
