Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes
Background/Aims: To investigate the effect of advanced glycation endproduct-induced autophagy in rat cardiomyocytes and to identify the role of autophagy in advanced glycation end product-induced cell apoptosis. Methods: After cultured rat cardiomyocytes were treated with advanced glycation end prod...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2015-09-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/430388 |
| _version_ | 1819074689645936640 |
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| author | Pengfei Hu Hui Zhou Ming Lu Liping Dou Gang Bo Jiale Wu Shuwei Huang |
| author_facet | Pengfei Hu Hui Zhou Ming Lu Liping Dou Gang Bo Jiale Wu Shuwei Huang |
| author_sort | Pengfei Hu |
| collection | DOAJ |
| description | Background/Aims: To investigate the effect of advanced glycation endproduct-induced autophagy in rat cardiomyocytes and to identify the role of autophagy in advanced glycation end product-induced cell apoptosis. Methods: After cultured rat cardiomyocytes were treated with advanced glycation end products (AGEs), protein expression was detected by western blotting, autophagosomes were observed by electron microscopy, the cell apoptotic rate was determined by flow cytometry, and cell variability was quantified by the MTT assay. Results: After cultured cardiomyocytes were treated with AGEs, the level of autophagy-associated protein LC3-II was up-regulated and SQSTM1/p62 was down-regulated; the number of autophagosomes was increased. Compared with the control group, the apoptotic rate of cardiomyocytes increased, and the cardiomyocyte viability was decreased in the AGE-treated group. Furthermore, pretreating cells with3-MA, an autophagy inhibitor, could enhance these effects. Treatment with AGEs activated phospho-ERK, phospho-JNK, and phospho-p38/MAPK but inhibited phospho-Akt and phospho-mTOR. Pretreatment with an ERK inhibitor and an Akt activator could inhibit AGE-induced autophagy, demonstrating that AGEs induce autophagy in cardiomyocytes through the ERK and Akt signalling pathways. Conclusion: AGEs can induce autophagy through the PI3K/AKT/mTOR and ERK signalling pathways and induce apoptosis through the PI3K/AKT/mTOR and p38/MAPK signalling pathways in rat cardiomyocytes. Autophagy plays a protective role in AGE-induced apoptosis in cardiomyocytes. |
| first_indexed | 2024-12-21T18:13:31Z |
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| id | doaj.art-d75aa5dfde6f4ce18fcbb8f516b44192 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-21T18:13:31Z |
| publishDate | 2015-09-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
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| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-d75aa5dfde6f4ce18fcbb8f516b441922022-12-21T18:54:44ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-09-0137269770610.1159/000430388430388Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in CardiomyocytesPengfei HuHui ZhouMing LuLiping DouGang BoJiale WuShuwei HuangBackground/Aims: To investigate the effect of advanced glycation endproduct-induced autophagy in rat cardiomyocytes and to identify the role of autophagy in advanced glycation end product-induced cell apoptosis. Methods: After cultured rat cardiomyocytes were treated with advanced glycation end products (AGEs), protein expression was detected by western blotting, autophagosomes were observed by electron microscopy, the cell apoptotic rate was determined by flow cytometry, and cell variability was quantified by the MTT assay. Results: After cultured cardiomyocytes were treated with AGEs, the level of autophagy-associated protein LC3-II was up-regulated and SQSTM1/p62 was down-regulated; the number of autophagosomes was increased. Compared with the control group, the apoptotic rate of cardiomyocytes increased, and the cardiomyocyte viability was decreased in the AGE-treated group. Furthermore, pretreating cells with3-MA, an autophagy inhibitor, could enhance these effects. Treatment with AGEs activated phospho-ERK, phospho-JNK, and phospho-p38/MAPK but inhibited phospho-Akt and phospho-mTOR. Pretreatment with an ERK inhibitor and an Akt activator could inhibit AGE-induced autophagy, demonstrating that AGEs induce autophagy in cardiomyocytes through the ERK and Akt signalling pathways. Conclusion: AGEs can induce autophagy through the PI3K/AKT/mTOR and ERK signalling pathways and induce apoptosis through the PI3K/AKT/mTOR and p38/MAPK signalling pathways in rat cardiomyocytes. Autophagy plays a protective role in AGE-induced apoptosis in cardiomyocytes.http://www.karger.com/Article/FullText/430388ApoptosisSignalling pathwaysAdvanced glycation end productsCardiomyocytesAutophagy |
| spellingShingle | Pengfei Hu Hui Zhou Ming Lu Liping Dou Gang Bo Jiale Wu Shuwei Huang Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes Cellular Physiology and Biochemistry Apoptosis Signalling pathways Advanced glycation end products Cardiomyocytes Autophagy |
| title | Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes |
| title_full | Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes |
| title_fullStr | Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes |
| title_full_unstemmed | Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes |
| title_short | Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes |
| title_sort | autophagy plays a protective role in advanced glycation end product induced apoptosis in cardiomyocytes |
| topic | Apoptosis Signalling pathways Advanced glycation end products Cardiomyocytes Autophagy |
| url | http://www.karger.com/Article/FullText/430388 |
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