Myofibrillogenesis Regulator 1 Rescues Renal Ischemia/Reperfusion Injury by Recruitment of PI3K-Dependent P-AKT to Mitochondria
| Autor: | Mi Liu, Hui-Min Mao, Xiao-Reng Wang, Tianqi Tao, Xiu-Hua Liu, Rui Ding, Yuan-Sheng Xie |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Renal cortex Muscle Proteins Myocardial Reperfusion Injury Mitochondrion Kidney Critical Care and Intensive Care Medicine Mitochondrial Membrane Transport Proteins Rats Sprague-Dawley Wortmannin 03 medical and health sciences Mitochondrial membrane transport protein chemistry.chemical_compound Internal medicine medicine Animals RNA Small Interfering biology Renal ischemia Mitochondrial Permeability Transition Pore Cytochromes c Kidney metabolism Mitochondria Rats Disease Models Animal 030104 developmental biology Endocrinology medicine.anatomical_structure Mitochondrial permeability transition pore chemistry Emergency Medicine biology.protein Cardiology Phosphatidylinositol 3-Kinase Proto-Oncogene Proteins c-akt |
| Zdroj: | Shock. 46:531-540 |
| ISSN: | 1073-2322 |
| DOI: | 10.1097/shk.0000000000000658 |
| Popis: | To investigate whether myofibrillogenesis regulator 1 (MR-1) attenuates renal ischemia/reperfusion (I/R) injury via inhibiting phosphorylated Akt (p-Akt) mitochondrial translocation-mediated opening of the mitochondrial permeability transition pore (mPTP), we injected adenovirus containing MR-1 gene or its siRNAs to the left kidney subcapsular areas of Sprague-Dawley rats, which subsequently underwent experimental renal I/R injury. Renal functions and the severity of the tubular injury were evaluated by the serum creatinine and blood urea nitrogen levels and the pathological scores. We also examined the mitochondrial morphology and functions. Total/p-Akt were assessed by western blot using the mitochondrial and the cytosolic fractions of cortex of renal tissue, respectively. We found that mitochondrial and cytosolic MR-1 levels and mitochondrial p-Akt decreased, and cytosolic p-Akt increased after reperfusion. Subcapsular injection of adenovirus led to higher MR-1 expression in the mitochondria/cytosol, inhibited mPTP opening, and alleviated renal I/R injury; adenovirus injection also upregulated mitochondrial total and p-Akt levels more prominently compared with the normal saline (NS) group. Subcapsular injection of MR-1 siRNAs significantly lowered MR-1 expression and induced renal injury, with increased mPTP opening and mitochondrial damage, similar to I/R injury. MR-1 interacted with Akt in renal cortex homogenate. Wortmannin, a phosphatidylinositol 3 kinase (PI3K) inhibitor, abolished both mitochondrial p-Akt recruitment and the protective effect of MR-1 overexpression on I/R injury. To conclude, MR-1 protects kidney against I/R injury through inhibiting mPTP opening and maintaining mitochondrial integrity, through the recruitment of PI3K-dependent p-Akt to the mitochondria. MR-1 could be a new therapeutic strategy for renal I/R injury. |
| Databáze: | OpenAIRE |
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