Effects of autophagy inhibitor 3-methyladenine on a diabetic mice model
AIM: To investigate the role of autophagy inhibitor 3-methyladenine (3-MA) on a diabetic mice model (DM) and the potential mechanism. METHODS: Male C57BL/6J mice were randomly divided into a normal control group (NC group) and an DM group. DM were induced by multiple low-dose intraperitoneal injecti...
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| Format: | Article |
| Language: | English |
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Press of International Journal of Ophthalmology (IJO PRESS)
2023-09-01
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| Series: | International Journal of Ophthalmology |
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| Online Access: | http://ies.ijo.cn/en_publish/2023/9/20230912.pdf |
| _version_ | 1797739551066685440 |
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| author | Hai-Wen Ren Wen Yu Ya-Nan Wang Xin-Yi Zhang Shun-Qiong Song Shu-Yu Gong Ling-Yao Meng Chen Gan Ben-Ju Liu Quan Gong |
| author_facet | Hai-Wen Ren Wen Yu Ya-Nan Wang Xin-Yi Zhang Shun-Qiong Song Shu-Yu Gong Ling-Yao Meng Chen Gan Ben-Ju Liu Quan Gong |
| author_sort | Hai-Wen Ren |
| collection | DOAJ |
| description | AIM: To investigate the role of autophagy inhibitor 3-methyladenine (3-MA) on a diabetic mice model (DM) and the potential mechanism. METHODS: Male C57BL/6J mice were randomly divided into a normal control group (NC group) and an DM group. DM were induced by multiple low-dose intraperitoneal injection of streptozotocin (STZ) 60 mg/kg●d for 5 consecutive days. DM mice were randomly subdivided into untreated group (DM group), 3-MA (10 mg/kg●d by gavage) treated group (DM+3-MA group) and chloroquine (CQ; 50 mg/kg by intraperitoneal injection) treated group (DM+CQ group). The fasting blood glucose (FBG) levels were recorded every week. At the end of experiment, retinal samples were collected. The expression levels of pro-apoptotic proteins cleaved caspase-3, cleaved poly ADP-ribose polymerase 1 (PARP1) and Bax, anti-apoptotic protein Bcl-2, fibrosis-associated proteins Fibronectin and type 1 collagen α1 chain (COL1A1), vascular endothelial growth factor (VEGF), inflammatory factors interleukin (IL)-1β and tumor necrosis factor (TNF)-α, as well as autophagy related proteins LC3, Beclin-1 and P62 were determined by Western blotting. The oxidative stress indicators 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) were detected by commercial kits. RESULTS: Both 3-MA and CQ had short-term hypoglycemic effect on FBG and reduced the expression of VEGF and inflammatory factors IL-1β and TNF-α in DM mice. 3-MA also significantly alleviated oxidative stress indicators 8-OHdG and MDA, decreased the expression of fibrosis-related proteins Fibronectin and COL1A1, pro-apoptotic proteins cleaved caspase-3, cleaved PARP1, as well as the ratio of Bax/Bcl-2. CQ had no significant impact on the oxidative stress indicators, fibrosis, and apoptosis related proteins. The results of Western blotting for autophagy related proteins showed that the ratio of LC3 II/LC3 I and the expression of Beclin-1 in the retina of DM mice were decreased by 3-MA treatment, and the expression of P62 was further increased by CQ treatment. CONCLUSION: 3-MA has anti-apoptotic and anti-fibrotic effects on the retina of DM mice, and can attenuate retinal oxidative stress, VEGF expression and the production of inflammatory factors in the retina of DM mice. The underlying mechanism of the above effects of 3-MA may be related to its inhibition of early autophagy and hypoglycemic effect. |
| first_indexed | 2024-03-12T13:59:49Z |
| format | Article |
| id | doaj.art-6e549112dd6047d59878e4d844f89294 |
| institution | Directory Open Access Journal |
| issn | 2222-3959 2227-4898 |
| language | English |
| last_indexed | 2024-03-12T13:59:49Z |
| publishDate | 2023-09-01 |
| publisher | Press of International Journal of Ophthalmology (IJO PRESS) |
| record_format | Article |
| series | International Journal of Ophthalmology |
| spelling | doaj.art-6e549112dd6047d59878e4d844f892942023-08-22T08:47:16ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982023-09-011691456146410.18240/ijo.2023.09.1220230912Effects of autophagy inhibitor 3-methyladenine on a diabetic mice modelHai-Wen Ren0Wen Yu1Ya-Nan Wang2Xin-Yi Zhang3Shun-Qiong Song4Shu-Yu Gong5Ling-Yao Meng6Chen Gan7Ben-Ju Liu8Quan Gong9Quan Gong. Department of Immunology, Medical School of Yangtze University, Jingzhou 434023, Hubei Province, China. gongquan1998@163.com; Ben-Ju Liu. Department of Human Anatomy, Medical School of Yangtze University, Jingzhou 434023, Hubei Province, China. liubenju1981@aliyun.comHealth Science Center, Yangtze University, Jingzhou 434023, Hubei Province, ChinaHealth Science Center, Yangtze University, Jingzhou 434023, Hubei Province, ChinaHealth Science Center, Yangtze University, Jingzhou 434023, Hubei Province, ChinaHealth Science Center, Yangtze University, Jingzhou 434023, Hubei Province, ChinaHealth Science Center, Yangtze University, Jingzhou 434023, Hubei Province, ChinaHealth Science Center, Yangtze University, Jingzhou 434023, Hubei Province, ChinaHealth Science Center, Yangtze University, Jingzhou 434023, Hubei Province, ChinaDepartment of Human Anatomy, Medical School of Yangtze University, Jingzhou 434023, Hubei Province, ChinaClinical Molecular Immunology Center, Medical School of Yangtze University, Jingzhou 434023, Hubei Province, China; Department of Immunology, Medical School of Yangtze University, Jingzhou 434023, Hubei Province, ChinaAIM: To investigate the role of autophagy inhibitor 3-methyladenine (3-MA) on a diabetic mice model (DM) and the potential mechanism. METHODS: Male C57BL/6J mice were randomly divided into a normal control group (NC group) and an DM group. DM were induced by multiple low-dose intraperitoneal injection of streptozotocin (STZ) 60 mg/kg●d for 5 consecutive days. DM mice were randomly subdivided into untreated group (DM group), 3-MA (10 mg/kg●d by gavage) treated group (DM+3-MA group) and chloroquine (CQ; 50 mg/kg by intraperitoneal injection) treated group (DM+CQ group). The fasting blood glucose (FBG) levels were recorded every week. At the end of experiment, retinal samples were collected. The expression levels of pro-apoptotic proteins cleaved caspase-3, cleaved poly ADP-ribose polymerase 1 (PARP1) and Bax, anti-apoptotic protein Bcl-2, fibrosis-associated proteins Fibronectin and type 1 collagen α1 chain (COL1A1), vascular endothelial growth factor (VEGF), inflammatory factors interleukin (IL)-1β and tumor necrosis factor (TNF)-α, as well as autophagy related proteins LC3, Beclin-1 and P62 were determined by Western blotting. The oxidative stress indicators 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) were detected by commercial kits. RESULTS: Both 3-MA and CQ had short-term hypoglycemic effect on FBG and reduced the expression of VEGF and inflammatory factors IL-1β and TNF-α in DM mice. 3-MA also significantly alleviated oxidative stress indicators 8-OHdG and MDA, decreased the expression of fibrosis-related proteins Fibronectin and COL1A1, pro-apoptotic proteins cleaved caspase-3, cleaved PARP1, as well as the ratio of Bax/Bcl-2. CQ had no significant impact on the oxidative stress indicators, fibrosis, and apoptosis related proteins. The results of Western blotting for autophagy related proteins showed that the ratio of LC3 II/LC3 I and the expression of Beclin-1 in the retina of DM mice were decreased by 3-MA treatment, and the expression of P62 was further increased by CQ treatment. CONCLUSION: 3-MA has anti-apoptotic and anti-fibrotic effects on the retina of DM mice, and can attenuate retinal oxidative stress, VEGF expression and the production of inflammatory factors in the retina of DM mice. The underlying mechanism of the above effects of 3-MA may be related to its inhibition of early autophagy and hypoglycemic effect.http://ies.ijo.cn/en_publish/2023/9/20230912.pdfdiabetic mellitus3-methyladenineautophagyfibrosisapoptosismice |
| spellingShingle | Hai-Wen Ren Wen Yu Ya-Nan Wang Xin-Yi Zhang Shun-Qiong Song Shu-Yu Gong Ling-Yao Meng Chen Gan Ben-Ju Liu Quan Gong Effects of autophagy inhibitor 3-methyladenine on a diabetic mice model International Journal of Ophthalmology diabetic mellitus 3-methyladenine autophagy fibrosis apoptosis mice |
| title | Effects of autophagy inhibitor 3-methyladenine on a diabetic mice model |
| title_full | Effects of autophagy inhibitor 3-methyladenine on a diabetic mice model |
| title_fullStr | Effects of autophagy inhibitor 3-methyladenine on a diabetic mice model |
| title_full_unstemmed | Effects of autophagy inhibitor 3-methyladenine on a diabetic mice model |
| title_short | Effects of autophagy inhibitor 3-methyladenine on a diabetic mice model |
| title_sort | effects of autophagy inhibitor 3 methyladenine on a diabetic mice model |
| topic | diabetic mellitus 3-methyladenine autophagy fibrosis apoptosis mice |
| url | http://ies.ijo.cn/en_publish/2023/9/20230912.pdf |
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