AI Article Synopsis
- - Sepsis can lead to damage in multiple organs, particularly through mitochondrial dysfunction, and the study focuses on how two proteins, SIRT1 and SIRT3, interact with this process in acute kidney injury (AKI) in a septic rat model.
- - Researchers found that sepsis reduced the activity of SIRT1 and SIRT3, increased levels of a damaged protein (ac-SOD2), and led to oxidative stress in kidney cells, indicating significant mitochondrial damage.
- - Treatment with resveratrol (RSV), which activates SIRT1, improved kidney function and survival rates by restoring SIRT1/3 activity; however, this positive effect was hindered by Ex527, a drug that inhibits SIRT
Article Abstract
Sepsis often results in damage to multiple organ systems, possibly due to severe mitochondrial dysfunction. Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage. The aim of this study was to determine the role of SIRT1/3 in acute kidney injury (AKI) following sepsis in a septic rat model. After drug pretreatment and cecal ligation and puncture (CLP) model reproduction in the rats, we performed survival time evaluation and kidney tissue extraction and renal tubular epithelial cell (RTEC) isolation. We observed reduced SIRT1/3 activity, elevated acetylated SOD2 (ac-SOD2) levels and oxidative stress, and damaged mitochondria in RTECs following sepsis. Treatment with resveratrol (RSV), a chemical SIRT1 activator, effectively restored SIRT1/3 activity, reduced acetylated SOD2 levels, ameliorated oxidative stress and mitochondrial function of RTECs, and prolonged survival time. However, the beneficial effects of RSV were greatly abrogated by Ex527, a selective inhibitor of SIRT1. These results suggest a therapeutic role for SIRT1 in the reversal of AKI in septic rat, which may rely on SIRT3-mediated deacetylation of SOD2. SIRT1/3 activation could therefore be a promising therapeutic strategy to treat sepsis-associated AKI.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5149703 | PMC |
| http://dx.doi.org/10.1155/2016/7296092 | DOI Listing |
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