SLC30A7 has anti-oxidant stress effects in high glucose-induced apoptosis via the NFE2L2/HMOX1 signal transduction pathway
| Autor: | Zhi-Hong Chi, Harvest F. Gu, Qijun Wan, Xiuli Zhang, Boxuan Yang, Tingwen Guan |
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| Rok vydání: | 2020 |
| Předmět: |
Male
HMOX1 NF-E2-Related Factor 2 Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Apoptosis Transfection ZINC TRANSPORTER 7 Antioxidants Diabetes Mellitus Experimental Pathogenesis 03 medical and health sciences Mice 0302 clinical medicine Endocrinology Western blot Internal Medicine Medicine Animals Humans Diabetic Nephropathies 030212 general & internal medicine medicine.diagnostic_test biology business.industry General Medicine NFE2L2 Cell biology Rats Glucose Heme Oxygenase (Decyclizing) biology.protein Signal transduction business Intracellular Signal Transduction |
| Zdroj: | Diabetes research and clinical practice. 172 |
| ISSN: | 1872-8227 |
| Popis: | Aims Apoptosis and oxidant stress are known to be involved in the pathogenesis of diabetic kidney disease (DKD). We have previously reported that zinc transporter 7 in SLC30 family (SLC30A7) inhibits apoptosis in rat peritoneal mesothelial cells under high glucose (HG) conditions. In the current study, we aimed to investigate whether SLC30A7 had effect for anti-oxidant stress in renal tubular epithelial cells under HG. Methods SLC30A7 in HG-induced apoptosis in a normal rat kidney tubular epithelial cell line (NRK-52E cells)/kidneys of STZ-induced diabetic mice was examined and the activity of nuclear factor erythroid 2-related factor 2 (NFE2L2) was further analyzed by using real time RT-PCR, siRNA and Western blot protocols. Results SLC30A7 was found to be up-regulated, while NFE2L2 was activated in kidneys of STZ-induced diabetic mice and HG-induced apoptosis of NRK-52E cells. Knock-down of SLC30A7 with siRNA protocol resulted in lower intracellular free zinc levels in the cells and decreased zinc distribution in the Golgi apparatus. Furthermore, knock-down of NFE2L2 down-regulated its target HMOX1 gene expression, decreased SLC30A7 activity but increased HG-induced apoptosis. Conclusion The current study provides new evidence that SLC30A7 has anti-oxidant stress effects in HG-induced apoptosis via the NFE2L2/HMOX1 signal transduction pathway. |
| Databáze: | OpenAIRE |
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