ROS-activated mitochondrial apoptosis is required for adipocyte differentiation:A revisit to the biological significance of apoptosis
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- 英文论文题名：ROS-activated mitochondrial apoptosis is required for adipocyte differentiation:A revisit to the biological significance of apoptosis
- 论文作者：王欣 ; 廖鼐 ; 王钊 ; 吴昊 ; 于卫华 ; 张涛 ; 海春旭
- 英文论文作者：Xin Wang ; Nai Liao ; Zhao Wang ; Hao Wu ; Weihua Yu ; Tao Zhang ; Chunxu Hai ; Department of Toxicology ; Shaanxi Key Lab of Free Radical Biology and Medicine ; the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment ; School of Public Health ; Fourth Military Medical University
- 年：2014
- 作者机构：第四军医大学军事预防医学院毒理学教研室/特殊作业环境危害评估与防治教育部重点实验室/陕西省自由基生物学与医学重点实验室;
- 英文论文关键词：apoptosis ; adipocyte differentiation ; ROS ; mitochondrial dysfunction
- 会议召开时间：2014-11-29
- 会议录名称：陕西省毒理学会2014年学术会议论文集
- 语种：英文
- 分类号：R589.2
- 学会代码：XBST
- 会议名称：陕西省毒理学会2014年学术会议
- 会议地点：中国陕西西安
- 主办单位：陕西省毒理学会
- 学会名称：西北大学生态毒理研究所
- 页数：11
- 文件大小：2976k
- 原文格式：O
- 会议级别：地方
摘要
Obesity has reached epidemic proportions world-wide,with more than a billion adults being overweight,and over 300 million adults classified as obese.Adipogenesis is the process of formation of new adipocytes from preadipocyte precursors,and an understanding of this process is important for control of obesity.Apoptosis is essential for various physiological processes and is involved in numerous pathophysiological conditions.Mitochondria play a central role in apoptosis,through releasing a number ofproapoptotic factors to cytosol,including cytochrome c(Cyto c),aif,smac/diablo,and endoG.These factors in turn activate a battery of enzymatic executors of apoptosis,leading to cleavage of proteins and DNA.In the present study,we investigated the role of apoptosis in adipocyte differentiation.The results showed that during the process of 3T3-L1 adipocyte differentiation,apoptosis increased significantly compared with preadipocytes,as evidenced by increased staining of TUNEL.Apoptosis activator 2 notably promoted adipocyte differentiation both in 3T3-L1preadipocytes and in adipose tissue of mice.Moreover,along with the differentiation of adipocyte,mitochondrial ROS increased and antioxidant NAC significantly decreased adipocyte differentiation.Mitochondrial protective agent CysA inhibited lipid accumulation in the course of adipocyte differentiation.These results demonstrated that mitochondrial apoptosis may play an important role in adipocyte differentiation.The data reminds us that besides cell death,apoptosis may play more important physiological roles in various processes.Since numerous environmental agents could induce apoptosis,the finds may provide a common mechanism of environmental agents-related obesity and disorder of lipid metabolism.
Obesity has reached epidemic proportions world-wide,with more than a billion adults being overweight,and over 300 million adults classified as obese.Adipogenesis is the process of formation of new adipocytes from preadipocyte precursors,and an understanding of this process is important for control of obesity.Apoptosis is essential for various physiological processes and is involved in numerous pathophysiological conditions.Mitochondria play a central role in apoptosis,through releasing a number of proapoptotic factors to cytosol,including cytochrome c(Cyto c),aif,smac/diablo,and endoG.These factors in turn activate a battery of enzymatic executors of apoptosis,leading to cleavage of proteins and DNA.In the present study,we investigated the role of apoptosis in adipocyte differentiation.The results showed that during the process of 3T3-L1 adipocyte differentiation,apoptosis increased significantly compared with preadipocytes,as evidenced by increased staining of TUNEL.Apoptosis activator 2 notably promoted adipocyte differentiation both in 3T3-L1 preadipocytes and in adipose tissue of mice.Moreover,along with the differentiation of adipocyte,mitochondrial ROS increased and antioxidant NAC significantly decreased adipocyte differentiation.Mitochondrial protective agent CysA inhibited lipid accumulation in the course of adipocyte differentiation.These results demonstrated that mitochondrial apoptosis may play an important role in adipocyte differentiation.The data reminds us that besides cell death,apoptosis may play more important physiological roles in various processes.Since numerous environmental agents could induce apoptosis,the finds may provide a common mechanism of environmental agents-related obesity and disorder of lipid metabolism.
Obesity has reached epidemic proportions world-wide,with more than a billion adults being overweight,and over 300 million adults classified as obese.Adipogenesis is the process of formation of new adipocytes from preadipocyte precursors,and an understanding of this process is important for control of obesity.Apoptosis is essential for various physiological processes and is involved in numerous pathophysiological conditions.Mitochondria play a central role in apoptosis,through releasing a number of proapoptotic factors to cytosol,including cytochrome c(Cyto c),aif,smac/diablo,and endoG.These factors in turn activate a battery of enzymatic executors of apoptosis,leading to cleavage of proteins and DNA.In the present study,we investigated the role of apoptosis in adipocyte differentiation.The results showed that during the process of 3T3-L1 adipocyte differentiation,apoptosis increased significantly compared with preadipocytes,as evidenced by increased staining of TUNEL.Apoptosis activator 2 notably promoted adipocyte differentiation both in 3T3-L1 preadipocytes and in adipose tissue of mice.Moreover,along with the differentiation of adipocyte,mitochondrial ROS increased and antioxidant NAC significantly decreased adipocyte differentiation.Mitochondrial protective agent CysA inhibited lipid accumulation in the course of adipocyte differentiation.These results demonstrated that mitochondrial apoptosis may play an important role in adipocyte differentiation.The data reminds us that besides cell death,apoptosis may play more important physiological roles in various processes.Since numerous environmental agents could induce apoptosis,the finds may provide a common mechanism of environmental agents-related obesity and disorder of lipid metabolism.
引文
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6.Spiegelman BM&Flier JS.Adipogenesis and obesity:rounding out the big picture.Cell 1996;87:377-389.
7.Krotkiewski M,Sjostrom L,Bjorntorp P,Carlgren G,Garellick G&Smith U.Adipose tissue cellularity in relation to prognosis for weight reduction.Int J Obes 1971;1:395-416.
8.Rosen ED&Spiegelman BM.Molecular regulation of adipogenesis.Annu Rev Cell Dev Biol 2000;16:145-171.
9.Rosen ED,Walkey CJ,Puigserver P&Spiegelman BM.Transcriptional regulation of adipogenesis.Genes Dev 2000;14:1293-1307.
10.Gregoire FM,Smas CM&Sul HS.Understanding adipocyte differentiation.Physiological Reviews1998;78:783-809.
11.Rosen ED&MacDougald OA.Adipocyte"differentiation from the inside out.Nat Rev Mol Cell Biol2006;7:885-896.
12.Farmer SR.Transcriptional control of adipocyte formation.Cell Metab 2006;4:263-273.
13.Lefterova MI&Lazar MA.New developments in adipogenesis.Trends Endocrinol Metab 2009;20:107-114.
14.Tontonoz P&Spiegelman BM.Fat and beyond:the diverse biology of PPARgamma.Annual Review Of Biochemistry 2008;77:289-312.
15.Tormos KV,Anso E,Hamanaka RB,Eisenbart J,Joseph J,Kalyanaraman B&Chandel NS.Mitochondrial ComplexⅢROS Regulate Adipocyte Differentiation.Cell Metabolism 2011;14:537-544.
16.Wang X,Bai H,Zhang X,Liu J,Cao P,Liao N,Zhang W,Wang Z&Hai C.Inhibitory effect of oleanolic acid on hepatocellular carcinoma via ERK-p53-mediated cell cycle arrest and mitochondrial-dependent apoptosis.Carcinogenesis 2013;34:1230-1323.
17.Bernardi P,Petronilli V,Di Lisa F&Forte M.A mitochondrial perspective on cell death.Trends In Biochemical Sciences 2001;26:112-117.
18.Scorrano L&Korsmeyer SJ.Mechanisms of cytochrome c release by proapoptotic BCL-2 family members.Biochem Biophys Res Commun 2003;304:437-444.
2.Ogden CL,Carroll MD,Kit BK&Flegal KM.Prevalence of obesity in the Unites States,2009-2010.NCHSData Brief 2012;82:1-8.
3.Kopelman PG.Obesity as a medical problem.Nature 2000;404:635-643.
4.Haslam DW&James WP.Obesity.Lancet 2005;366:1197-1209.
5.Bjorntorp P&Sjostrom L.Number and size of adipose tissue fat cells in relation to metabolism in human obesity.Metabolism-Clinical And Experimental 1971;20:703-713.
6.Spiegelman BM&Flier JS.Adipogenesis and obesity:rounding out the big picture.Cell 1996;87:377-389.
7.Krotkiewski M,Sjostrom L,Bjorntorp P,Carlgren G,Garellick G&Smith U.Adipose tissue cellularity in relation to prognosis for weight reduction.Int J Obes 1971;1:395-416.
8.Rosen ED&Spiegelman BM.Molecular regulation of adipogenesis.Annu Rev Cell Dev Biol 2000;16:145-171.
9.Rosen ED,Walkey CJ,Puigserver P&Spiegelman BM.Transcriptional regulation of adipogenesis.Genes Dev 2000;14:1293-1307.
10.Gregoire FM,Smas CM&Sul HS.Understanding adipocyte differentiation.Physiological Reviews1998;78:783-809.
11.Rosen ED&MacDougald OA.Adipocyte"differentiation from the inside out.Nat Rev Mol Cell Biol2006;7:885-896.
12.Farmer SR.Transcriptional control of adipocyte formation.Cell Metab 2006;4:263-273.
13.Lefterova MI&Lazar MA.New developments in adipogenesis.Trends Endocrinol Metab 2009;20:107-114.
14.Tontonoz P&Spiegelman BM.Fat and beyond:the diverse biology of PPARgamma.Annual Review Of Biochemistry 2008;77:289-312.
15.Tormos KV,Anso E,Hamanaka RB,Eisenbart J,Joseph J,Kalyanaraman B&Chandel NS.Mitochondrial ComplexⅢROS Regulate Adipocyte Differentiation.Cell Metabolism 2011;14:537-544.
16.Wang X,Bai H,Zhang X,Liu J,Cao P,Liao N,Zhang W,Wang Z&Hai C.Inhibitory effect of oleanolic acid on hepatocellular carcinoma via ERK-p53-mediated cell cycle arrest and mitochondrial-dependent apoptosis.Carcinogenesis 2013;34:1230-1323.
17.Bernardi P,Petronilli V,Di Lisa F&Forte M.A mitochondrial perspective on cell death.Trends In Biochemical Sciences 2001;26:112-117.
18.Scorrano L&Korsmeyer SJ.Mechanisms of cytochrome c release by proapoptotic BCL-2 family members.Biochem Biophys Res Commun 2003;304:437-444.