Effects of high-intensity aerobic exercise during multiple cycles of doxorubicin treatment on cardiac catabolism

Figure 1.. High-intensity aerobic exercise during doxorubicin treatment significantly reduces body weight and absolute heart weight. (A) Schematic representation of the experimental design, illustrating the timing of doxorubicin administration, the duration, and the protocol for exercise. (B-D) Graphs depicting changes in body weight, absolute heart weight, and the ratio of absolute heart weight-to-body weight across experimental groups following doxorubicin treatment with concurrent exercise (n = 7 per group). Asterisks (*) denote statistically significant differences between experimental groups (p < 0.05). EXE, exercise; DOX, doxorubicin.

Figure 2.. High-intensity aerobic exercise mitigates DOX-induced defects in autophagic flux. (A) Representative Western blot images illustrating the protein expression of key components within the autophagy pathway. Ponceau S staining confirms equal protein loading. (B-I) Quantitative analysis of protein levels for LC3-II, LC3-I, the LC3-II/LC3-I ratio, ATG7, p62, LAMP2, Cathepsin L, and BNIP3. Data are presented as the mean ± SEM (n = 7 per group). Asterisks (*) denote statistically significant differences between experimental groups (p < 0.05). EXE, exercise; DOX, doxorubicin; SED, sedentary; SAL, saline; SEM, standard error of the mean.

Figure 3.. High-intensity aerobic exercise modulates upstream regulators of autophagy. (A) Representative images of Western blots showing key proteins of autophagy-regulating AMPK/ULK1 signaling pathways. Ponceau S staining confirmed equal protein loading. (B-G) Protein quantification of p-AMPKαThr172, AMPKα, p-AMPKαThr172/AMPKα ratio, p-ULK1Ser555, ULK1, and p-ULK1Ser555/ULK1 ratio. Data are presented as the mean ± SEM (n = 7 per group). Asterisks (*) indicate significant differences between ex perimental groups (p < 0.05). EXE, exercise; DOX, doxorubicin; SED, sedentary; SAL, saline; SEM, standard error of the mean.

Figure 4.. High-intensity aerobic exercise accelerates DOX-induced extracellular matrix and cardiac protein catabolism. (A) Representative Western blot images displaying the protein expression of key markers related to the extracellular matrix and the ubiquitin-proteasome system (UPS) pathway. (B-D) Quantitative analysis of protein levels for β-actin, Talin, and Cleaved α-spectrin II. (E-J) Quantitative analysis of protein levels for MuRF1, MAFbx, K48-linked polyubiquitin, PSMC1, PSMA1, and PSMB5. Data are presented as the mean ± SEM (n = 7 per group). Asterisks (*) indicate statistically significant differences between experimental groups (p < 0.05). EXE, exercise; DOX, doxorubicin; SED, sedentary; SAL, saline; SEM, standard error of the mean.

Figure 5.. High-intensity aerobic exercise between multiple cycles of DOX treatment improves lipid metabolism. (A) Representative Western blot images showing the protein expression of key enzymes involved in lipolysis. (B-I) Quantitative analysis of protein levels for p-ACC, total ACC, the p-ACC/ACC ratio, FASN, DGAT, CPT1B, ACADVL, and HADHSC. Data are presented as the mean ± SEM (n = 7 per group). Asterisks (*) denote statistically significant differences between experimental groups (p < 0.05). EXE, exercise; DOX, doxorubicin; SED, sedentary; SAL, saline; ACC, Acetyl-CoA Carboxylase; FASN, fatty acid synthase; DGAT, diglyceride acyltransferase; CPT1B, carnitine palmitoyltransferase 1B; ACADVL, Acyl-CoA Dehydrogenase Very Long Chain; HADHSC, 3-Hydroxyacyl-CoA dehydrogenase.