Sodium Ferulate Prevents Daunorubicin--Induced Apoptosis in H9c2 Cells via Inhibition of the ERKs Pathway.
BACKGROUND
Daunorubicin (DNR)-induced cardiotoxicity, which is closely associated with cardiomyocyte apoptosis, limits the drug's clinical application. The activation of the extracellular regulated protein kinases (ERKs) pathway is responsible for the pro-apoptosis effect of DNR Sodium ferulate (SF) has recently been found to attenuate both DNR-induced cardiotoxicity and mitochondrial apoptosis in juvenile rats. Nonetheless, the precise mechanism underlying SF-induced cardio-protection remains unclear.


METHODS
The DNR-injured H9c2 cell model was prepared by incubating the cells in 1 µM DNR for 24 h. Amounts of 15.6, 31.3 or 62.5 µM SF were simultaneously added to the cells. The effect of SF on the cytotoxic and apoptotic parameters of the cells was studied by monitoring apoptosis regulation via the ERKs pathway.


RESULTS
SF attenuated DNR-induced cell death (particularly apoptotic death), cTnI and β-tubulin degradation, and cellular morphological changes. SF reduced mitochondrial membrane potential depolarization, cytochrome c leakage, and caspase-9 and caspase-3 activation. SF also decreased ERK1/2, phospho-ERK1/2, p53 and Bax expression and increased Bcl-2 expression. These effects were similar to the results observed when using the pharmacological ERKs phosphorylation inhibitor, AZD6244.


CONCLUSIONS
We determined that SF protects H9c2 cells from DNR-induced apoptosis through a mechanism that involves the interruption of the ERKs signaling pathway.
Department of Physiology & Pathophysiology and Laboratory of Cardiovascular Sciences, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, People's Republic of China.
Zhi-Juan
ZJ
Wu
Jing
J
Yu
Qiu-Juan
QJ
Fang
Rui-Xing
RX
Wang
Jia-Bian
JB
Lian
Rui-Lan
RL
He
Hai-Xia
HX
Jiao
Mo-Jun
MJ
Lin
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003373:Coumaric Acids / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D003630:Daunorubicin / Q000009:adverse effects*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D051381:Rats; D019210:Troponin I / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C517975:AZD 6244; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D003373:Coumaric Acids; D019210:Troponin I; D014404:Tubulin; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C004999:ferulic acid; D048049:Extracellular Signal-Regulated MAP Kinases; D053453:Caspase 9; D003630:Daunorubicin