The changes of reactive oxygen species and glutathione by MG132, a proteasome inhibitor affect As4.1 juxtaglomerular cell growth and death |
| |
| Authors: | Yong Hwan Han Woo Hyun Park |
| |
| Institution: | 1. Department of Pediatrics, Department of Pathology, Tulane University School of Medicine, New Orleans, LA 70112, USA;2. Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA;1. Department of Nephrology, Shenzhen People''s Hospital, Second Clinical Medical College, Jinan University, Shenzhen, China;2. Shenzhen People''s Hospital, Second Clinical Medical College, Jinan University, Shenzhen, China;3. Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China;4. Department of Rehabilitation, Chancheng District Central Hospital of Foshan City, Foshan, China;1. Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei Province, China;2. Department of Electromyogram, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China;1. College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, China;2. School of Environmental Science and Technology, Shanghai Jiao Tong University, Shanghai, 200240, China;3. NUS Environmental Research Institute, Singapore;3. Key Laboratories of Food Safety Research;4. Key Laboratories of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China;5. Shanghai Xuhui Central Hospital, Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai 200031, China;6. Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200031, China;12. Model Animal Research Center, and Ministry of Eduction Key Laboratory of Model Animals for Disease Study, Nanjing University, Nanjing 210061, China;1. Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan;2. Division of Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan |
| |
| Abstract: | The proteasome inhibitor MG132 has been shown to induce apoptotic cell death through the formation of reactive oxygen species (ROS). Here, we evaluated the effects of MG132 on the growth and death of As4.1 juxtaglomerular cells in relation to ROS and glutathione (GSH) levels. MG132 inhibited the growth of As4.1 cells with an IC50 of approximately 0.3–0.4 μM at 48 h and induced cell death, which was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨm), Bcl-2 decrease, activation of caspase-3 and -8, and PARP cleavage. MG132 increased intracellular ROS levels including O2 ? and GSH depleted cell numbers. N-acetyl cysteine (NAC, a well-known antioxidant) significantly decreased ROS level and GSH depleted cell numbers in MG132-treated As4.1 cells, along with the prevention of cell growth inhibition, cell death and MMP (ΔΨm) loss. NAC also decreased the caspase-3 activity of MG132. l-Buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) or diethyldithiocarbamate (DDC; an inhibitor of Cu/Zn-SOD) did not affect cell growth, death, ROS and GSH levels in MG132-treated As4.1 cells. Conclusively, MG132 reduced the growth of As4.1 cells via apoptosis. The changes of ROS and GSH by MG132 were involved in As4.1 cell growth and death. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
