Objective: This study mainly analyzes the mechanism of SIRT3 alleviating sepsis-induced acute lung injury (ALI) by regulating the deacetylation of FoxO3a and inhibiting pyroptosis.
Methods: SIRT3-overexpressing and silenced BEAS-2B cells were used to evaluate the effect of SIRT3 on apoptosis in LPS-treated lung epithelial cells. FoxO3a-silenced BEAS-2B cells were also used to verify the mechanism by which SIRT3 inhibited oxidative stress and pyroptosis in vitro in ALI. 3-TYP was used to inhibit the deacetylation function of SIRT3 in vivo. Pyroptosis was assessed by detecting GSDMD-N and LDH efflux.
Results: In CLP-induced ALI mice, GSDMD-N and LDH levels were elevated, pyroptosis was induced. Silencing of SIRT3 exacerbated oxidative stress, NLRP3 activation and pyroptosis, and inhibited the deacetylation of FoxO3a. Overexpression of SIRT3 attenuated pyroptosis, induced deacetylation and restored the expression of FoxO3a and MnSOD. Silencing FoxO3a aggravated pyroptosis. Overexpression of SIRT3 restored the reduced FoxO3a expression and suppressed pyroptosis. 3-TYP blocked the promotion of FoxO3a by SIRT3 and the inhibitory effect of SIRT3 on pyroptosis.
Conclusion: The reduction of SIRT3 in sepsis caused hyperacetylation of FoxO3a, which in turn exacerbates oxidative stress and induces pyroptosis of ALI. Increasing the level of SIRT3 promotes FoxO3a through deacetylation, thereby inhibiting pyroptosis and relieving ALI.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.pupt.2023.102244 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
MCC950 mitigates SIRT3-NLRP3-driven inflammation and rescues post-stroke neurogenesis.
Biomed Pharmacother
January 2025
Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Sarfarazganj, Lucknow 226003, India; Department of Stem Cell Biology and Regenerative Medicine, Era's Lucknow Medical College Hospital, Era University, Sarfarazganj, Lucknow 226003, India. Electronic address:
Sustained activation of the SIRT3-NLRP3 inflammasome has been associated with worse outcomes after ischemic stroke. The objective of this study was to examine the potential mechanism by which the SIRT3-NLRP3 inflammasome affects neural stem and progenitor cells (NSPCs) after transient middle cerebral artery occlusion (tMCAO) in rats. Following tMCAO, significantly elevated levels of NLRP3, ASC, cleaved caspase 1, IL-1β, and IL-18 were observed in the ischemic subventricular zone.
View Article and Find Full Text PDFRespiratory complex I-mediated NAD regeneration regulates cancer cell proliferation through the transcriptional and translational control of p21 expression by SIRT3 and SIRT7.
Mol Oncol
January 2025
Division of Cancer Cell Biology, Department of Pharmaceutical Sciences, Showa University Graduate School of Pharmacy, Tokyo, Japan.
The role of the electron transport chain (ETC) in cell proliferation control beyond its crucial function in supporting ATP generation has recently emerged. In this study, we found that, among the four ETC complexes, the complex I (CI)-mediated NAD regeneration is important for cancer cell proliferation. In cancer cells, a decrease in CI activity by RNA interference (RNAi) against NADH:ubiquinone oxidoreductase core subunit V1 (NDUFV1) arrested the cell cycle at the G/S phase, accompanying upregulation of p21 cyclin-dependent kinase inhibitor expression.
View Article and Find Full Text PDFIdentification of mitophagy-related key genes and their correlation with immune cell infiltration in acute myocardial infarction via bioinformatics analysis.
Front Cardiovasc Med
January 2025
Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China.
Background: Acute myocardial infarction (AMI), a subset of acute coronary syndrome, remains the major cause of mortality worldwide. Mitochondrial dysfunction is critically involved in AMI progression, and mitophagy plays a vital role in eliminating damaged mitochondria. This study aimed to explore mitophagy-related biomarkers and their potential molecular basis in AMI.
View Article and Find Full Text PDFBlast-Overpressure Induced Modulation of PARP-SIRT-NRF2 Axis in Stress Signaling of Astrocytes and Microglia.
Immun Inflamm Dis
January 2025
Department of Medical Biochemistry, Institute of Health, Dambi Dollo University, Dambi Dolo, Ethiopia.
Background: The pathomechanism of blast traumatic brain injury (TBI) and blunt TBI is different. In blast injury, evidence indicates that a single blast exposure can often manifest long-term neurological impairments. However, its pathomechanism is still elusive, and treatments have been symptomatic.
View Article and Find Full Text PDFIsovitexin targets SIRT3 to prevent steroid-induced osteonecrosis of the femoral head by modulating mitophagy-mediated ferroptosis.
Bone Res
January 2025
The Department of Orthopedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
The death of osteoblasts induced by glucocorticoid (GC)-mediated oxidative stress plays a crucial role in the development of steroid-induced osteonecrosis of the femoral head (SIONFH). Improving bone formation driven by osteoblasts has shown promising outcomes in the prognosis of SIONFH. Isovitexin has demonstrated antioxidant properties, but its therapeutic effects on GC-induced oxidative stress and SIONFH remain unexplored.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!