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Compound Tinglizi Decoction-Containing Serum Is Associated with Inhibition of PANoptosis in Cardiomyocytes via SIRT3-Related Chaperone-Mediated Autophagy of AIM2

Year: 2025

Type: article

Abstract: Background: Septic cardiomyopathy (SCM) is a life-threatening complication of sepsis with no specific therapeutic options. Recent evidence suggests that PANoptosis, a programmed cell death pathway, contributes to myocardial injury in sepsis. Compound Tinglizi Decoction (CTLZC), a traditional Chinese herbal formula, has shown potential cardioprotective effects, yet the underlying biochemical mechanisms remain unclear. Methods: A rat model of SCM was established to investigate the effect of CTLZC-containing serum on myocardial injury. Primary cardiomyocytes were treated with CTLZC-containing serum, and SIRT3 expression was modulated via overexpression and knockdown plasmids. Cell viability, PANoptosis markers, and chaperone-mediated autophagy (CMA) proteins were assessed through CCK-8, TUNEL staining, RT-qPCR, Western blotting, ELISA, and Co-IP assays. Results: CTLZC-containing serum enhanced cardiomyocyte viability and significantly upregulated SIRT3 expression. It inhibited the expression of PANoptosis-related molecules (AIM2, ZBP1, RIPK1, RIPK3, FADD, and caspase-8) and promoted the expression of CMA-related proteins HSC70 and LAMP2A. SIRT3 knockdown reversed these effects and increased the release of biochemical markers of myocardial injury (LDH, CK-MB) and inflammatory cytokines (TNF-α, IL-1β, IL-18). Co-IP confirmed that AIM2 interacts with HSC70, indicating lysosomal degradation via CMA. Conclusion: CTLZC-containing serum attenuates inflammatory and cell death responses in septic cardiomyopathy, likely through a SIRT3-associated modulation of chaperone-mediated autophagy and PANoptosis. These findings highlight the biochemical regulatory role of SIRT3 in mediating autophagic and inflammatory pathways during SCM, offering new insights into potential therapeutic targets.

Source: International Journal of General Medicine

DOI: 10.2147/ijgm.s540452