Mitochondrial outer membrane voltage-dependent anion channel is involved in renal dysfunction in a spontaneously hypertensive rat carrying transfer RNA mutations
| Autor: | Yang Li, Huanwan Yang, Yuqi Liu, Liuyang Tian, Chao Zhu, Pu Chen |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Mitochondrial DNA Voltage-dependent anion channel Blood Pressure Kidney Cell Line 03 medical and health sciences Adenosine Triphosphate 0302 clinical medicine Spontaneously hypertensive rat RNA Transfer Rats Inbred SHR Internal medicine medicine Animals bcl-2-Associated X Protein Membrane Potential Mitochondrial Pharmacology Membrane potential chemistry.chemical_classification Reactive oxygen species ATP synthase biology Chemistry Voltage-Dependent Anion Channel 1 Rats Oxygen Protein Transport 030104 developmental biology Endocrinology Gene Expression Regulation Mitochondrial Membranes Mutation biology.protein Reactive Oxygen Species Bacterial outer membrane VDAC1 030217 neurology & neurosurgery |
| Zdroj: | European Journal of Pharmacology. 865:172622 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2019.172622 |
| Popis: | Mitochondrial DNA mutations promote hypertensive renal dysfunction, but the molecular mechanism remains unclear. This study compared renal damage between spontaneously hypertensive rats (SHR) and SHR with mitochondrial transfer (t)RNA mutations. To investigate the role of mitochondrial outer membrane voltage-dependent anion channel 1 (VDAC1) in the process of tRNA-promoting mitochondrial dysfunction, we treated HK-2 cells with H2O2, cyclosporine (CsA), or atractylodin (Atr) to observe the association between VDAC1 and mitochondrial function. Intriguingly, the mitochondrial structure of SHR carrying tRNA mutations was obviously disordered, and reactive oxygen species production and VDAC1 and Bax expression and binding were increased, which was associated with marked renal dysfunction. The expression of VDAC1 and Bax was also up-regulated in HK-2 cells by H2O2 treatment. However, CsA and Atr had no significant effect on the expression of VDAC1 and Bax. H2O2 caused mitochondrial membrane potential collapse, while CsA could increase the mitochondrial membrane potential and Atr had the opposite effect. Treatment with H2O2 significantly decreased ATP synthesis, which was improved by intervention with Atr. H2O2 also decreased the maximum oxygen consumption rate, while CsA and Atr had no significant effect. We found that H2O2 promoted the colocalization of VDAC1 and Bax, which was partially inhibited by intervention with CsA or Atr. In conclusion, we found that tRNA mutations promoted hypertensive renal insufficiency. Increased reactive oxygen species was an important associated mechanism, which inhibited mitochondrial function by affecting VDAC1 expression and function. |
| Databáze: | OpenAIRE |
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