Background:Wnt/β-catenin signal has been reported to exert cytoprotective effects in cellular models of several diseases,including Parkinson’s disease(PD).This study aimed to investigate the neuroprotective effects ...Background:Wnt/β-catenin signal has been reported to exert cytoprotective effects in cellular models of several diseases,including Parkinson’s disease(PD).This study aimed to investigate the neuroprotective effects of actived Wnt/β-catenin signal by Wnt3a on SH-SY5Y cells treated with 6-hydroxydopamine(6-OHDA).Methods:Wnt3a-conditioned medium(Wnt3a-CM)was used to intervene dopaminegic SH-SY5Y cells treated with 6-OHDA.Cell toxicity was determined by cell viability and lactate dehydrogenase leakage(LDH)assay.The mitochondria function was measured by the mitochondrial membrane potential,while oxidative stress was monitored with intracellular reactive oxygen species(ROS).Western blot analysis was used to detect the expression of GSK3β,β-catenin as well as Akt.Results:Our results showed that 100μM 6-OHDA treated for 24 h significantly decreased cell viability and mitochondrial transmembrane potential,reduced the level ofβ-catenin and p-Akt,increased LDH leakage,ROS production and the ratio of p-GSK3β(Tyr216)to p-GSK3β(Ser9).However,Wnt3a-conditioned medium reversing SH-SY5Y cells against 6-OHDA-induced neurotoxicity by reversing these changes.Conclusions:Activating of Wnt/β-catenin pathway by Wnt3a-CM attenuated 6-OHDA-induced neurotoxicity significantly,which related to the inhibition of oxidative stress and maintenance of normal mitochondrial function.展开更多
The aim of this review is to explore the role of mitochondria in regulating macrophage sterol homeostasis and inflammatory responses within the aetiology of atherosclerosis.Macrophage generation of oxysterol activator...The aim of this review is to explore the role of mitochondria in regulating macrophage sterol homeostasis and inflammatory responses within the aetiology of atherosclerosis.Macrophage generation of oxysterol activators of liver X receptors(LXRs),via sterol 27-hydroxylase,is regulated by the rate of flux of cholesterolto the inner mitochondrial membrane,via a complex of cholesterol trafficking proteins.Oxysterols are key signalling molecules,regulating the transcriptional activity of LXRs which coordinate macrophage sterol metabolism and cytokine production,key features influencing the impact of these cells within atherosclerotic lesions.The precise identity of the complex of proteins mediating mitochondrial cholesterol trafficking in macrophages remains a matter of debate,but may include steroidogenic acute regulatory protein and translocator protein.There is clear evidence that targeting either of these proteins enhances removal of cholesterol via LXRα-dependent induction of ATP binding cassette transporters(ABCA1,ABCG1) and limits the production of inflammatory cytokines; interventions which influence mitochondrial structure and bioenergetics also impact on removal of cholesterol from macrophages.Thus,molecules which can sustain or improve mitochondrial structure,the function of the electron transport chain,or increase the activity of components of the protein complex involved in cholesterol transfer,may therefore have utility in limiting or regressing atheroma development,reducing the incidence of coronary heart disease and myocardial infarction.展开更多
Objective To investigate the toxicity of cigarette smoke extract (CSE) and nicotine on mouse brain mitochondria as well as the protective effect of vitamin C in vitro. Method Mouse brain mitochondria in vitro was incu...Objective To investigate the toxicity of cigarette smoke extract (CSE) and nicotine on mouse brain mitochondria as well as the protective effect of vitamin C in vitro. Method Mouse brain mitochondria in vitro was incubated with CSE or nicotine in the absence or presence of vitamin C for 60 minutes, and the changes of mitochondrial function and structure were measured. Results CSE inhibited mitochondrial ATPase and cytochrome C oxidase activities in a dose-dependent manner. However, no significant changes in the peroxidation indices were observed when mitochondrial respiratory enzymes activity was inhibited, and protection of mitochondria from CSE-induced injury by vitamin C was not displayed in vitro. The effect of CSE on mouse brain mitochondria swelling response to calcium stimulation was dependent on calcium concentrations. CSE inhibited swelling of mitochondria at 6.5μmol/L Ca2+, but promoted swelling response at 250μmol/L Ca2+. Nicotine, the major component of cigarette smoke, showed no significant damage in mouse brain mitochondria in vitro. The CSE treatment induced mitochondrial inner membrane damage and vacuolization of the matrix, whereas the outer mitochondrial membrane appeared to be preserved. Conclusion The toxic effect of CSE on brain mitochondria may be due to its direct action on enzymatic activity rather than through oxygen free radical injury. Nicotine is not the responsible component for the toxicity of CSE to brain mitochondria.展开更多
Mammalian mitochondria are sensitive targets of cytotoxic effect of superoxide and nitric oxide (NO).In this study we measured mitochondrial state 3, 4 respiration, respiratory control rate (RCR) and phosphor-oxygen r...Mammalian mitochondria are sensitive targets of cytotoxic effect of superoxide and nitric oxide (NO).In this study we measured mitochondrial state 3, 4 respiration, respiratory control rate (RCR) and phosphor-oxygen ratio (P/O) to evaluate mitochondrial respiratory function (MRF) in cerebral ischemia and at 1, 3, 6, 24 and 48 h after reperfusion. We also observed the changes of MRF after giving N-nitro L- arginine (LNA) at various times. MRF was inhibited 30 min after cerebral ischemia. The major change was decrease in RCR, especially in the case of state 3 respiration. In the early stage of reperfusion, MRF recovered and state 3 was higher than the level of normal control. In later stage of reperfusion (at 6 h), obvious increase in state 4 led to decrease in RCR again. RCR was higher than that of reperfusion control by decreasing of state 4 when LNA was given at 1 h after reperfusion and 5 h thereafter; there were no change in MRF when LNA was given at the beginning of reperfusion. We concluded that MRF was further damaged, and ineffective oxygen consumption increased after reperfusion; LNA could protect MRF after reperfusion. Overproduction of endogenous NO has pathologic toxicity to mitochondria at 1- 2 h after reperfusion.展开更多
基金by Nature Science Foundation of China(81401058,81401645,81271428 and 81471292)a grant from the State Key Development Program for Basic Research of China(2011CB510000)+1 种基金a grant from Medical Scientific Research Foundation of Guangdong Province(B2014139)a grant supported by assisting research project of science and technology for Xinjiang(201591160).
文摘Background:Wnt/β-catenin signal has been reported to exert cytoprotective effects in cellular models of several diseases,including Parkinson’s disease(PD).This study aimed to investigate the neuroprotective effects of actived Wnt/β-catenin signal by Wnt3a on SH-SY5Y cells treated with 6-hydroxydopamine(6-OHDA).Methods:Wnt3a-conditioned medium(Wnt3a-CM)was used to intervene dopaminegic SH-SY5Y cells treated with 6-OHDA.Cell toxicity was determined by cell viability and lactate dehydrogenase leakage(LDH)assay.The mitochondria function was measured by the mitochondrial membrane potential,while oxidative stress was monitored with intracellular reactive oxygen species(ROS).Western blot analysis was used to detect the expression of GSK3β,β-catenin as well as Akt.Results:Our results showed that 100μM 6-OHDA treated for 24 h significantly decreased cell viability and mitochondrial transmembrane potential,reduced the level ofβ-catenin and p-Akt,increased LDH leakage,ROS production and the ratio of p-GSK3β(Tyr216)to p-GSK3β(Ser9).However,Wnt3a-conditioned medium reversing SH-SY5Y cells against 6-OHDA-induced neurotoxicity by reversing these changes.Conclusions:Activating of Wnt/β-catenin pathway by Wnt3a-CM attenuated 6-OHDA-induced neurotoxicity significantly,which related to the inhibition of oxidative stress and maintenance of normal mitochondrial function.
文摘The aim of this review is to explore the role of mitochondria in regulating macrophage sterol homeostasis and inflammatory responses within the aetiology of atherosclerosis.Macrophage generation of oxysterol activators of liver X receptors(LXRs),via sterol 27-hydroxylase,is regulated by the rate of flux of cholesterolto the inner mitochondrial membrane,via a complex of cholesterol trafficking proteins.Oxysterols are key signalling molecules,regulating the transcriptional activity of LXRs which coordinate macrophage sterol metabolism and cytokine production,key features influencing the impact of these cells within atherosclerotic lesions.The precise identity of the complex of proteins mediating mitochondrial cholesterol trafficking in macrophages remains a matter of debate,but may include steroidogenic acute regulatory protein and translocator protein.There is clear evidence that targeting either of these proteins enhances removal of cholesterol via LXRα-dependent induction of ATP binding cassette transporters(ABCA1,ABCG1) and limits the production of inflammatory cytokines; interventions which influence mitochondrial structure and bioenergetics also impact on removal of cholesterol from macrophages.Thus,molecules which can sustain or improve mitochondrial structure,the function of the electron transport chain,or increase the activity of components of the protein complex involved in cholesterol transfer,may therefore have utility in limiting or regressing atheroma development,reducing the incidence of coronary heart disease and myocardial infarction.
文摘Objective To investigate the toxicity of cigarette smoke extract (CSE) and nicotine on mouse brain mitochondria as well as the protective effect of vitamin C in vitro. Method Mouse brain mitochondria in vitro was incubated with CSE or nicotine in the absence or presence of vitamin C for 60 minutes, and the changes of mitochondrial function and structure were measured. Results CSE inhibited mitochondrial ATPase and cytochrome C oxidase activities in a dose-dependent manner. However, no significant changes in the peroxidation indices were observed when mitochondrial respiratory enzymes activity was inhibited, and protection of mitochondria from CSE-induced injury by vitamin C was not displayed in vitro. The effect of CSE on mouse brain mitochondria swelling response to calcium stimulation was dependent on calcium concentrations. CSE inhibited swelling of mitochondria at 6.5μmol/L Ca2+, but promoted swelling response at 250μmol/L Ca2+. Nicotine, the major component of cigarette smoke, showed no significant damage in mouse brain mitochondria in vitro. The CSE treatment induced mitochondrial inner membrane damage and vacuolization of the matrix, whereas the outer mitochondrial membrane appeared to be preserved. Conclusion The toxic effect of CSE on brain mitochondria may be due to its direct action on enzymatic activity rather than through oxygen free radical injury. Nicotine is not the responsible component for the toxicity of CSE to brain mitochondria.
文摘Mammalian mitochondria are sensitive targets of cytotoxic effect of superoxide and nitric oxide (NO).In this study we measured mitochondrial state 3, 4 respiration, respiratory control rate (RCR) and phosphor-oxygen ratio (P/O) to evaluate mitochondrial respiratory function (MRF) in cerebral ischemia and at 1, 3, 6, 24 and 48 h after reperfusion. We also observed the changes of MRF after giving N-nitro L- arginine (LNA) at various times. MRF was inhibited 30 min after cerebral ischemia. The major change was decrease in RCR, especially in the case of state 3 respiration. In the early stage of reperfusion, MRF recovered and state 3 was higher than the level of normal control. In later stage of reperfusion (at 6 h), obvious increase in state 4 led to decrease in RCR again. RCR was higher than that of reperfusion control by decreasing of state 4 when LNA was given at 1 h after reperfusion and 5 h thereafter; there were no change in MRF when LNA was given at the beginning of reperfusion. We concluded that MRF was further damaged, and ineffective oxygen consumption increased after reperfusion; LNA could protect MRF after reperfusion. Overproduction of endogenous NO has pathologic toxicity to mitochondria at 1- 2 h after reperfusion.
