Senescence in human AC16 cardiac cells is associated with thymidine kinase induction and histone loss.

Abstract

AC16 cells are a transformed human cardiac cell line commonly used to study cardiomyocyte biology. We show that reduced proliferation and senescence markers can be robustly induced in AC16 cells cultured in low serum condition and treated with (i) low-dose doxorubicin, (ii) UV 254 nm, or (iii) H 2 O 2 exposure for up to 48 hours. Increased p21 (CDKN1A) and H2A.X variant histone (H2AX) levels serve as reliable molecular markers upon all three treatment conditions, but the up-regulation of another common senescence marker, p16 (CDKN2A) was not observed. A proteomics screen further shows that the loss of histones and the increased expression of thymidine kinases (TK1) are prominent features of AC16 cells under doxorubicin induced senescence.