Fig. 4: DOX activates cardiac autophagy, and GSDMD promotes myocardial autophagy levels. | Cell Death & Disease

Fig. 4: DOX activates cardiac autophagy, and GSDMD promotes myocardial autophagy levels.

From: Gasdermin D mediates endoplasmic reticulum stress via FAM134B to regulate cardiomyocyte autophagy and apoptosis in doxorubicin-induced cardiotoxicity

Fig. 4

A, B Temporal changes in GSDMD (FL and N teminals), LC3II (microtubule-associated protein 1A/1B-light chain 3) protein levels. N = 3 per group. C PCR analysis of autophagy-related-genes (Atg4, Atg5, Atg7, Atg10, Atg12, Atg16, Beclin-1, Bnip-3, LC3B, Sqstm1, Gabarapl1, and TFEB) in mouse hearts at 0, 1, 3, 5, and 7 days after DOX injection. N = 3 per group. D, E Representative western blots of LC3 in DOX-induced GSDMD(flox/flox) and GSDMD-CKO hearts or AAV9-NC and AAV9-GSDMD-OE hearts. N = 6 for former groups and n = 3 for later groups. F, G Representative western blots of LC3 in DOX-induced GSDMD(flox/flox) and GSDMD-CKO hearts or AAV9-NC and AAV9- GSDMD-OE hearts with or without BAFA1. N = 3 per group. BAFA1 treatment, 2.5 mg/kg, intraperitoneal injection 2 h before the surgery. H Analysis of LC3II protein expression in GSDMD(flox/flox) and GSDMD-CKO or AAV9-NC and AAV9-GSDMD-OE hearts in acute DOX model. N = 6 for GSDMD(flox/flox) and GSDMD-CKO mice group, n = 3 for AAV9-NC and AAV9-GSDMD-OE groups. I Statistics of LC3II protein expression in different mice groups treated with DOX and/or BafA1. N = 3 per group. J, K Representative electron micrograph images of murine cardiac muscle derived from mice treated with DOX. Magnified section showing ultrastructural defects including autophagosomes and autolysosomes. (scale bar: 2 μm or 1 μm). Data are depicted as the mean ± SEM. Statistical significance was determined by one-way and two-way ANOVA with a post hoc Holm–Sidak test, ns not significant; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

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