Journal
EXPERT OPINION ON THERAPEUTIC TARGETS
Volume 20, Issue 6, Pages 645-652Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/14728222.2016.1177023
Keywords
Deacetylation; hemorrhagic shock; intestinal injury; mitochondrial dysfunction; SIRT3; SOD2
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Funding
- President Foundation of Nanfang Hospital, Southern Medical University (Guangzhou, China) [2015C005, 2015Z001]
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Background: Previously, we demonstrated that sirtuin (SIRT) 1 plays vital roles in the small intestine (SI), protecting against severe hemorrhagic shock (HS), and that polydatin (PD) can attenuate SI injury via SIRT1 activation. Objective: To explore the role of SIRT3 and mitochondria in SI injury after HS, and explore SIRT3 as a therapeutic target of PD in HS. Methods: An H2O2-induced model of oxidative stress and an HS model were created in IEC-6 cells and Sprague-Dawley rats, respectively. Protein content and activity of SIRT1/3 and SOD2, acetylated-SOD2 level, and mitochondrial morphology/function were determined. Results: Expression and activity of SIRT1/3 were reduced in SI tissue and IEC-6 cells after HS or oxidative stress, accompanied by an increased acetylated-SOD2 level and damaged mitochondria. Treatment with PD or resveratrol restored SIRT1/3 activity considerably, restored SIRT1/3 expression slightly, and reduced acetylated-SOD2 levels, which lead to elevated SOD2 activity and ameliorated mitochondrial function. The addition of 3-TYP (SIRT3 inhibitor) partially blocked the mitochondrial-protective effects of PD, but did not affect increased SIRT1 activity. Conclusions: The SIRT3-SOD2 signaling pathway is involved in mitochondrial dysfunction induced by HS. PD attenuates mitochondrial dysfunction via activation of the SIRT3-SOD2 pathway, and may be a new approach for HS treatment.
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