Metabolism of hydrogen peroxide in the course of embryonic development ofsilkworm (variety Guang) was determined by using colorimetric analysis and oxygen electrodemethod. The results indicated that: 1) In the course ...Metabolism of hydrogen peroxide in the course of embryonic development ofsilkworm (variety Guang) was determined by using colorimetric analysis and oxygen electrodemethod. The results indicated that: 1) In the course of fertilization (0-4 h after egg laying), thelevel of H_2O_2 content reached its peak value at 2.5 h of the developmental course and the activity ofsuperoxidase dismutase (SOD) was at higher level while the activity of catalase (CAT) at the lowestcorrespondingly; 2) The H_2O_2 content in embryo, in which the diapause of eggs was being relievedthrough treatment with hydrochloric acid on time in the course of embryonic development, wassignificantly higher than that of diapause eggs except the lower level showed in the embryo whenthe development of it went on for 168~216 h and the activity of SOD reached, lower and higher,tWo peaks in 72 and 168 h after egg-laying, respectively, and was significantly higher in late stagewhile the activity of CAT was shown with a stable level in the period of 72-192 h after egg-laying,and, after then, a rapid rising occurred in the embryo. The level of the CAT activity in embryowas shown significantly lower than that in diapause eggs in early period and higher in late stage ofegg development; 3) In the course of formation of diapause in eggs, the level of H_2O_2contentchanged smoothly and the activity of SOD changed vigorously in early period, and kept stable statelater; and the CAT activity increased gradually; while in the course of relief of diapause under ontime-treatment with hydrochloric acid, the level of H_2O_2 was significantly higher than that indiapause eggs and the SOD activity displayed a new peak value and significantly rose in later stage,while the activity of CAT in relieving embryo from diapause was signincantly lower than that indiapause eggs. Combining the results obtained in other researches with those from ours mentionedabove, we suggest that the metabolism of H_2O_2 might be of importance in the courses of formationand relief of diapause in silkworm eggs. Maybe the esterase A4 timer hypothesis and themicropylar barrier to oxygen hypothesis could be integrated for explanation of the course offormation and relief of diapause in silkworm eggs.展开更多
Objective To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.Methods Male intraut...Objective To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.Methods Male intrauterine growth restriction(IUGR) offspring induced by maternal protein-malnutrition and normal controls were studied.The body weights of offspring rats were weighted from birth to 12 weeks of age.Fasting plasma glucose and insulin levels were determined by glucose oxidase method and enzyme-linked immunosorbent assay(ELISA) respectively at 1 week,8 weeks,and 12 weeks.Peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase) mRNA and protein levels in liver were measured by real time RT-PCR and Western blot in newborn rats(Week 1) and adult rats(Week 12).Results Birth weights of IUGR rats were significantly lower than those of controls until 4 weeks later,when IUGR rats caught up to controls.Between 8 and 12 weeks,the growth of IUGR rats surpassed that of controls.No significant differences were observed in blood glucose and insulin levels at newborn rats between the two groups.However,by the end of 8 weeks IUGR rats developed hyperinsulinemia and high insulin resistance index.At the age of 12 weeks,IUGR rats had mild fasting hyperglycemia.In addition,hepatic PGC-1α mRNA and protein levels as well as hepatic mRNA levels of PEPCK and G6Pase at Week 1 and Week 12 in IUGR rats were all significantly higher than those of controls(P<0.05).Conclusions As a result of intrauterine malnutrition,the expression of gluconeogenic genes is exaggerated in offspring.This change stays through adulthood and may contribute to the pathogenesis of type 2 diabetes.展开更多
Objective: To explore the molecular regulation mechanism of carvedilol in attenuating the reversion back towards fetal energy metabolism during the development of cardiac hypertrophy induced by coarctation of abdomina...Objective: To explore the molecular regulation mechanism of carvedilol in attenuating the reversion back towards fetal energy metabolism during the development of cardiac hypertrophy induced by coarctation of abdominal aorta (CAA) in male Wistar rats. Methods: Hemodynamic and ventricular remodeling parameters, free fatty acid content in the serum were measured in the experimental animals at 16 weeks after the surgical CAA, the rats receiving carvedilol intervention (CAR) after CAA, and those with sham operation (SH). The expressions of muscle carnitine palmitoyltransferaseⅠ (M-CPTⅠ) and medium chain acyl-CoA dehydrogenase (MCAD) mRNA in the cardiac myocytes from every group were studied with RT-PCR. Results: Significant left ventricular hypertrophy were observed in the rats 16 weeks after coarctation operation (P<0.05), together with significant free fatty acids accumulation and downregulation of M-CPTⅠ and MCAD mRNA (P<0.05) in CAA group. Carvedilol at a dose of 30 mg/kg/d for 12 weeks inhibited the left ventricular hypertrophy induced by pressure overload and enhanced the gene expressions of rate-limiting enzyme (M-CPTⅠ) and key enzyme of fatty acid (MCAD) in the CAR group compared with CAA group (P<0.05). Conclusion: Pressure overload-induced hypertrophy in CAA rats causes the reversion back towards fetal enery metabolism, that is, downregulates the expressions of rate-limiting enzyme and key enzyme of fatty acid oxidation. The intervention therapy with carvedilol, a vasodilating alpha- and beta-adrenoreceptor antagonist, attenuates the reversion of the metabolic gene expression to fetal type through upregulating M-CPTⅠ and MCAD mRNA expressions. Thus, carvedilol may exert cardioprotective effects on heart failure by the mechanism of preserving the adult metabolic gene regulation.展开更多
In order to investigate glucose metabolism pathways and their changes in Kunming mouse preimplantation 1-,2-,4-,8-cell,and morula embryos,the mRNA level for the genes involved in glucose metabolism was tested by neste...In order to investigate glucose metabolism pathways and their changes in Kunming mouse preimplantation 1-,2-,4-,8-cell,and morula embryos,the mRNA level for the genes involved in glucose metabolism was tested by nested RT-PCR on embryos at different development stages in vivo.These genes were glucose 6-phosphate dehydrogenase(G6PDH),phospho-fructokinase(PFK),and phosphoglucomutase(PGM),representing pentose phosphate pathway(PPP),glycolysis,and glycogensis and glycogenolysis respectively.Three sets of inner and outer primers were designed and synthesized based on cDNA sequences of G6PDH,PFK and PGM.RT-PCR results revealed that G6PDH gene transcription was found in Kunming mouse 1-8 cell embryos,and not in morula embryos;it indicated that 1-8 cell embryos may metabolize glucose by pentose phosphate pathway,but morula embryos can not do so.PFK gene transcription was found in 1-8 cell and morula embryos;it is probable that there exists glycolysis in those embryos.PGM gene transcription was not found in 1-8 cell and morula embryos,so glycogenesis and glycogenolysis in these embryos were not present.展开更多
Caffeine is a substance presented in foods such as coffee, tea, soft drinks, chocolates and medicines and is commonly consumed by pregnant women. Due to its ability to cross the placental membrane and accumulate in th...Caffeine is a substance presented in foods such as coffee, tea, soft drinks, chocolates and medicines and is commonly consumed by pregnant women. Due to its ability to cross the placental membrane and accumulate in the fetus body, caffeine and its metabolites have been contraindicated or recommended in small doses during pregnancy. Studies in rodents relate caffeine intake to lower rates of fertilization, embryonic implantation, changes in placental structure, increased occurrence of low fetal and placental weights, abortion and stillbirth. However, in humans, studies involving caffeine consumption are inconclusive. Methodological complexity, difficulty for measuring caffeine intake and ethical reasons are limiting factors for a more accurate conclusion. So far, caffeine recommendation ranges from 100 to 300 mg/day. Even though researches have recommended low caffeine consumption by pregnant women in order to avoid deleterious consequences during gestation, a safe dose has not been established until now. The aim of the present review is to describe the main findings on the effects of caffeine consumption during pregnancy in both human and rodent experimental models.展开更多
Primary ovarian insufficiency(POI) occurs in about 1% of female population under the age of 40,leading to reproductive problems,an earlier encounter with menopausal symptoms,and complicated diseases.There are three pr...Primary ovarian insufficiency(POI) occurs in about 1% of female population under the age of 40,leading to reproductive problems,an earlier encounter with menopausal symptoms,and complicated diseases.There are three presumable mechanisms involved in the development of POI,namely apoptosis acceleration,follicular maturation blocking and premature follicle activation,through the following studied causes:(i) chromosomal abnormalities or gene mutations:mostly involve X chromosome,such as FMR1 premutation;more and more potentially causal genes have been screened recently;(ii) metabolic disorders such as classic galactosaemia and 17-OH deficiency;(iii) autoimmune mediated ovarian damage:observed alone or with some certain autoimmune disorders and syndromes;but the specificity and sensitivity of antibodies towards ovary are still questionable;(iv) iatrogenic:radiotherapy or chemotherapy used in cancer treatment,as well as pelvic surgery with potential threat to ovaries' blood supply can directly damage ovarian function;(v) virus infection such as HIV and mumps;(vi) toxins and other environmental/lifestyle factors:cigarette smoking,toxins(e.g.,4-vinylcyclohexene diepoxide),and other environmental factors are associated with the development of POI.The etiology of a majority of POI cases is not identified,and is believed to be multifactorial.Strategies to POI include hormone replacement and infertility treatment.Assisted conception with donated oocytes has been proven to achieve pregnancy in POI women.Embryo cryopreservation,ovarian tissue cryopreservation and oocyte cryopreservation have been used to preserve ovarian reserve in women undergoing cancer treatments.展开更多
Enhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells.However,little is known about its regulatory roles in gene expression and cell fate determination.Here,we confirm that gly...Enhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells.However,little is known about its regulatory roles in gene expression and cell fate determination.Here,we confirm that glycolytic metabolism and lactate production decrease during the differentiation of mouse embryonic stem cells(mESCs).Importantly,acidic pH due to lactate accumulation can transiently prevent the silencing of mESC self-renewal in differentiation conditions.Furthermore,acidic pH partially blocks the differentiation of human ESCs(hESCs).Mechanistically,acidic pH downregulates AGO1 protein and de-represses a subset of mRNA targets of miR-290/302 family of microRNAs which facilitate the exit of naive pluripotency state in mESCs.Interestingly,AGO1 protein is also downregulated by acidic pH in cancer cells.Altogether,this study provides insights into the potential function and underlying mechanism of acidic pH in pluripotent stem cells(PSCs).展开更多
文摘Metabolism of hydrogen peroxide in the course of embryonic development ofsilkworm (variety Guang) was determined by using colorimetric analysis and oxygen electrodemethod. The results indicated that: 1) In the course of fertilization (0-4 h after egg laying), thelevel of H_2O_2 content reached its peak value at 2.5 h of the developmental course and the activity ofsuperoxidase dismutase (SOD) was at higher level while the activity of catalase (CAT) at the lowestcorrespondingly; 2) The H_2O_2 content in embryo, in which the diapause of eggs was being relievedthrough treatment with hydrochloric acid on time in the course of embryonic development, wassignificantly higher than that of diapause eggs except the lower level showed in the embryo whenthe development of it went on for 168~216 h and the activity of SOD reached, lower and higher,tWo peaks in 72 and 168 h after egg-laying, respectively, and was significantly higher in late stagewhile the activity of CAT was shown with a stable level in the period of 72-192 h after egg-laying,and, after then, a rapid rising occurred in the embryo. The level of the CAT activity in embryowas shown significantly lower than that in diapause eggs in early period and higher in late stage ofegg development; 3) In the course of formation of diapause in eggs, the level of H_2O_2contentchanged smoothly and the activity of SOD changed vigorously in early period, and kept stable statelater; and the CAT activity increased gradually; while in the course of relief of diapause under ontime-treatment with hydrochloric acid, the level of H_2O_2 was significantly higher than that indiapause eggs and the SOD activity displayed a new peak value and significantly rose in later stage,while the activity of CAT in relieving embryo from diapause was signincantly lower than that indiapause eggs. Combining the results obtained in other researches with those from ours mentionedabove, we suggest that the metabolism of H_2O_2 might be of importance in the courses of formationand relief of diapause in silkworm eggs. Maybe the esterase A4 timer hypothesis and themicropylar barrier to oxygen hypothesis could be integrated for explanation of the course offormation and relief of diapause in silkworm eggs.
基金Supported by the National Natural Science Foundation of China(30672237)
文摘Objective To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.Methods Male intrauterine growth restriction(IUGR) offspring induced by maternal protein-malnutrition and normal controls were studied.The body weights of offspring rats were weighted from birth to 12 weeks of age.Fasting plasma glucose and insulin levels were determined by glucose oxidase method and enzyme-linked immunosorbent assay(ELISA) respectively at 1 week,8 weeks,and 12 weeks.Peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase) mRNA and protein levels in liver were measured by real time RT-PCR and Western blot in newborn rats(Week 1) and adult rats(Week 12).Results Birth weights of IUGR rats were significantly lower than those of controls until 4 weeks later,when IUGR rats caught up to controls.Between 8 and 12 weeks,the growth of IUGR rats surpassed that of controls.No significant differences were observed in blood glucose and insulin levels at newborn rats between the two groups.However,by the end of 8 weeks IUGR rats developed hyperinsulinemia and high insulin resistance index.At the age of 12 weeks,IUGR rats had mild fasting hyperglycemia.In addition,hepatic PGC-1α mRNA and protein levels as well as hepatic mRNA levels of PEPCK and G6Pase at Week 1 and Week 12 in IUGR rats were all significantly higher than those of controls(P<0.05).Conclusions As a result of intrauterine malnutrition,the expression of gluconeogenic genes is exaggerated in offspring.This change stays through adulthood and may contribute to the pathogenesis of type 2 diabetes.
文摘Objective: To explore the molecular regulation mechanism of carvedilol in attenuating the reversion back towards fetal energy metabolism during the development of cardiac hypertrophy induced by coarctation of abdominal aorta (CAA) in male Wistar rats. Methods: Hemodynamic and ventricular remodeling parameters, free fatty acid content in the serum were measured in the experimental animals at 16 weeks after the surgical CAA, the rats receiving carvedilol intervention (CAR) after CAA, and those with sham operation (SH). The expressions of muscle carnitine palmitoyltransferaseⅠ (M-CPTⅠ) and medium chain acyl-CoA dehydrogenase (MCAD) mRNA in the cardiac myocytes from every group were studied with RT-PCR. Results: Significant left ventricular hypertrophy were observed in the rats 16 weeks after coarctation operation (P<0.05), together with significant free fatty acids accumulation and downregulation of M-CPTⅠ and MCAD mRNA (P<0.05) in CAA group. Carvedilol at a dose of 30 mg/kg/d for 12 weeks inhibited the left ventricular hypertrophy induced by pressure overload and enhanced the gene expressions of rate-limiting enzyme (M-CPTⅠ) and key enzyme of fatty acid (MCAD) in the CAR group compared with CAA group (P<0.05). Conclusion: Pressure overload-induced hypertrophy in CAA rats causes the reversion back towards fetal enery metabolism, that is, downregulates the expressions of rate-limiting enzyme and key enzyme of fatty acid oxidation. The intervention therapy with carvedilol, a vasodilating alpha- and beta-adrenoreceptor antagonist, attenuates the reversion of the metabolic gene expression to fetal type through upregulating M-CPTⅠ and MCAD mRNA expressions. Thus, carvedilol may exert cardioprotective effects on heart failure by the mechanism of preserving the adult metabolic gene regulation.
基金National Natural Science Foundation of China(39600106)
文摘In order to investigate glucose metabolism pathways and their changes in Kunming mouse preimplantation 1-,2-,4-,8-cell,and morula embryos,the mRNA level for the genes involved in glucose metabolism was tested by nested RT-PCR on embryos at different development stages in vivo.These genes were glucose 6-phosphate dehydrogenase(G6PDH),phospho-fructokinase(PFK),and phosphoglucomutase(PGM),representing pentose phosphate pathway(PPP),glycolysis,and glycogensis and glycogenolysis respectively.Three sets of inner and outer primers were designed and synthesized based on cDNA sequences of G6PDH,PFK and PGM.RT-PCR results revealed that G6PDH gene transcription was found in Kunming mouse 1-8 cell embryos,and not in morula embryos;it indicated that 1-8 cell embryos may metabolize glucose by pentose phosphate pathway,but morula embryos can not do so.PFK gene transcription was found in 1-8 cell and morula embryos;it is probable that there exists glycolysis in those embryos.PGM gene transcription was not found in 1-8 cell and morula embryos,so glycogenesis and glycogenolysis in these embryos were not present.
文摘Caffeine is a substance presented in foods such as coffee, tea, soft drinks, chocolates and medicines and is commonly consumed by pregnant women. Due to its ability to cross the placental membrane and accumulate in the fetus body, caffeine and its metabolites have been contraindicated or recommended in small doses during pregnancy. Studies in rodents relate caffeine intake to lower rates of fertilization, embryonic implantation, changes in placental structure, increased occurrence of low fetal and placental weights, abortion and stillbirth. However, in humans, studies involving caffeine consumption are inconclusive. Methodological complexity, difficulty for measuring caffeine intake and ethical reasons are limiting factors for a more accurate conclusion. So far, caffeine recommendation ranges from 100 to 300 mg/day. Even though researches have recommended low caffeine consumption by pregnant women in order to avoid deleterious consequences during gestation, a safe dose has not been established until now. The aim of the present review is to describe the main findings on the effects of caffeine consumption during pregnancy in both human and rodent experimental models.
文摘Primary ovarian insufficiency(POI) occurs in about 1% of female population under the age of 40,leading to reproductive problems,an earlier encounter with menopausal symptoms,and complicated diseases.There are three presumable mechanisms involved in the development of POI,namely apoptosis acceleration,follicular maturation blocking and premature follicle activation,through the following studied causes:(i) chromosomal abnormalities or gene mutations:mostly involve X chromosome,such as FMR1 premutation;more and more potentially causal genes have been screened recently;(ii) metabolic disorders such as classic galactosaemia and 17-OH deficiency;(iii) autoimmune mediated ovarian damage:observed alone or with some certain autoimmune disorders and syndromes;but the specificity and sensitivity of antibodies towards ovary are still questionable;(iv) iatrogenic:radiotherapy or chemotherapy used in cancer treatment,as well as pelvic surgery with potential threat to ovaries' blood supply can directly damage ovarian function;(v) virus infection such as HIV and mumps;(vi) toxins and other environmental/lifestyle factors:cigarette smoking,toxins(e.g.,4-vinylcyclohexene diepoxide),and other environmental factors are associated with the development of POI.The etiology of a majority of POI cases is not identified,and is believed to be multifactorial.Strategies to POI include hormone replacement and infertility treatment.Assisted conception with donated oocytes has been proven to achieve pregnancy in POI women.Embryo cryopreservation,ovarian tissue cryopreservation and oocyte cryopreservation have been used to preserve ovarian reserve in women undergoing cancer treatments.
基金This work was supported by the National Key Research and Development Program of China(2016YFA0100701 and 2018YFA0107601)the National Natural Science Foundation of China(91640116,91940302,31622033,and 31821091)the Fundamental Research Funds for the Central Universities(3332018008).
文摘Enhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells.However,little is known about its regulatory roles in gene expression and cell fate determination.Here,we confirm that glycolytic metabolism and lactate production decrease during the differentiation of mouse embryonic stem cells(mESCs).Importantly,acidic pH due to lactate accumulation can transiently prevent the silencing of mESC self-renewal in differentiation conditions.Furthermore,acidic pH partially blocks the differentiation of human ESCs(hESCs).Mechanistically,acidic pH downregulates AGO1 protein and de-represses a subset of mRNA targets of miR-290/302 family of microRNAs which facilitate the exit of naive pluripotency state in mESCs.Interestingly,AGO1 protein is also downregulated by acidic pH in cancer cells.Altogether,this study provides insights into the potential function and underlying mechanism of acidic pH in pluripotent stem cells(PSCs).