Silibinin protects rat cardiac myocyte from isoproterenol-induced DNA damage independent on regulation of cell cycle.
Silibinin, derived from the milk thistle plant, Silybum marianum, has been traditionally used as an antihepatotoxic agent for the treatment of liver disease. Our preliminary study demonstrated that silibinin has protected rat cardiac myocytes against beta-adrenergic agonist isoproterenol-induced injury through resuming mitochondrial function and regulating the expression of SIRT1 and Bcl-2 family members. In this study, we investigate whether silibinin has anti-apoptotic effect on isoproterenol-treated rat cardiac myocytes. DNA damage, detected by the TUNEL and DNA fragmentation assay, was diminished after treatment of silibinin. Results of nitrite and Western blot assays showed that the amount of NO and the expression of iNOS were decreased after treatment with silibinin, while the expression of procaspase-3 and digestion of caspase-3 substrates, the inhibitor of caspase-activated DNase (ICAD) and poly-(ADP-ribose) polymerase (PARP), were increased simultaneously. The DNA damage was reversed by down-regulation of p53 phosphorylation after treatment with silibinin. Result of flowcytometric analysis showed that the cell cycle was not affected, and the expression of cell cycle regulatory protein p21 also had no change. Consequently, silibinin protected cardiac myocytes against isoproterenol-induced DNA damage through caspase pathway and the expression of p53, but independent on regulation of cell cycle.
Zhou
Bei
B
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, China.
Wu
Li-Jun
LJ
Tashiro
Shin-ichi
S
Onodera
Satoshi
S
Uchiumi
Fumiaki
F
Ikejima
Takashi
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology; D004249:DNA Damage; D007545:Isoproterenol / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012838:Silymarin; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D000077385:Silybin; D020169:Caspases; D007545:Isoproterenol