Table 2.
Downstream targets of SIRT1 that are regulated during DOX-induced cardiotoxicity
| Substrate | Animal or cell model | DOX dose | Treatment period | Functions of SIRT1 | Mechanism | Reference |
|---|---|---|---|---|---|---|
| PGC-1α | C57BL/6 mice and H9c2 cells | 20 mg/kg (cumulative dose) and 1 μM | 6 days and 24 h | Antioxidation and regulate mitochondrial function | Deacetylate PGC-1α | [97] |
| Human cardiomyocyte AC16 cells | 125 nM | 24 h | Regulate mitochondrial function and biogenesis | Deacetylate PGC-1α | [95] | |
| AMPK | 129S1/SvlmJ mice and H9c2 cells | 20 mg/kg (cumulative dose) and 5 μg/ml | 4 weeks and 22 h | Anti-inflammation, antioxidation and anti-apoptosis | Deacetylate LKB1 and activate AMPK | [105] |
| p53 | Balb/c mice | 24 mg/kg (cumulative dose) | 3 weeks | Anti-apoptosis | Deacetylate p53 | [110] |
| H9c2 cells | 1 μM | 24 h | Anti-apoptosis | Deacetylate p53 | [111] | |
| p66Shc | Sprague–Dawley rats | 16 mg/kg or 32 mg/kg (cumulative dose) | 4 or 8 weeks | Anti-apoptosis | Suppress p66Shc expression | [116] |
| Sprague–Dawley rats | 20 mg/kg (cumulative dose) | 9 days | Regulate mitochondrial function, antioxidation and anti-apoptosis | Suppress p66Shc expression | [117] | |
| NF-κB | C57BL/6 mice | 15 mg/kg (single dose) or 15 mg/kg (cumulative dose) | 8 days or 6 weeks | Anti-inflammation | Suppress nuclear translocation of NF-κB | [86] |
|
p38 MAPK |
C57BL/6 mice | 20 mg/kg (single dose) | 5 days | Antioxidation and anti-apoptosis | Suppress p38 MAPK expression | [129] |
| FOXOs | H9c2 cells | 5 μM | 24 h | Anti-apoptosis | Suppress FOXO1 expression | [136] |
| TGF-β | Fischer 344 rats | 15 mg/kg (cumulative dose) | 2 weeks | Anti-fibrosis | Suppress TGF-β/SMAD3 pathway | [88] |
| NLRP3 | Sprague–Dawley rats and H9c2 cells | 15 mg/kg (cumulative dose) and 5 μM | 6 weeks and 24 h | Anti-inflammation | Suppress the NLRP3 inflammasome | [23] |
| Kunming mice and H9c2 cells | 15 mg/kg (single dose) and 5 μM | 7 days and 24 h | Anti-inflammation | Suppress the NLRP3 inflammasome | [151] |
SIRT1 Sirtuin 1, DOX doxorubicin, PGC-1α peroxisome proliferator-activated receptor gamma coactivator-1 alpha, LKB1 liver kinase B1, AMPK AMP-activated protein kinase, p53 tumor protein p53, NF-κB nuclear factor kappa B, MAPK mitogen-activated protein kinase, FOXO forkhead box O, TGF-β transforming growth factor-beta, NLRP3 NOD-like receptor family pyrin domain-containing protein 3, H9c2 cells rat cardiomyocyte cell line, SMAD3 mothers against decapentaplegic homolog 3