Insufficient fumarase contributes to hypertension by an imbalance of redox metabolism in Dahl salt-sensitive rats
| Autor: | Pengfei Yang, Mingyu Liang, Zhongmin Tian, Xuewei Zheng, Yanan Ouyang, Zhe Yang, Xinrui Zhao, Entai Hou, Meng Chen, Xiaoxue Li |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Antioxidant Proteome Physiology medicine.medical_treatment Glutathione reductase 030204 cardiovascular system & hematology Cell Line Fumarate Hydratase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal Medicine medicine Animals Humans Mitochondrial respiratory chain complex I 030212 general & internal medicine chemistry.chemical_classification Reactive oxygen species Rats Inbred Dahl Chemistry Glutathione peroxidase Glutathione Biochemistry Fumarase Hypertension OGDH Cardiology and Cardiovascular Medicine Reactive Oxygen Species Oxidation-Reduction |
| Zdroj: | Hypertension research : official journal of the Japanese Society of Hypertension. 42(11) |
| ISSN: | 1348-4214 |
| Popis: | Fumarase insufficiencies can increase reactive oxygen species (ROS). This study will further dissect the imbalance of redox metabolism and the mechanism of ROS production using proteomic technology in fumarase knockdown HK-2 cells. The contribution of fumarase was further confirmed by supplementation of fumarate and malate in Dahl salt-sensitive rats. Proteomic analysis indicated that fumarase knockdown in HK-2 cells changed the expression or activity of NADPH oxidase (NOX), mitochondrial respiratory chain Complex I and III, ATP synthase subunits, and α-oxoglutarate dehydrogenase (OGDH). Meanwhile, the activities of key antioxidant enzymes, including glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione reductase, glutathione peroxidase, and glutathione S-transferase, increased significantly. The apparent activation of antioxidant defense appeared insufficient as the glutathione and GSH/GSSG ratio were decreased significantly. Dahl salt-sensitive rats exhibited changes in redox metabolism similar to HK-2 cells with fumarase knockdown. Supplementation with fumarate and malate increased and decreased, respectively, blood pressure and H2O2 and malondialdehyde in salt-sensitive rats. These results indicated that insufficient fumarase activity increased ROS by regulating NOX, Complex I and III, ATPase alpha, and OGDH and the imbalance of glutathione metabolism, which may be one of the main reasons for salt-sensitive hypertension. Malate may be a potentially effective drug for the prevention and treatment of salt-sensitive hypertension. |
| Databáze: | OpenAIRE |
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