Apoptosis-suppressing and autophagy-promoting effects of calpain on oridonin-induced L929 cell death.
Calpain, calcium-dependent cysteine protease, is reported here to impose the crucial influence on oridonin-induced L929 cell apoptosis and autophagy. We found that inhibition of calpain increased oridonin-induced Bax activation, cytochrome c release and PARP cleavage, indicating that calpain plays an anti-apoptotic role in oridonin-induced L929 cell apoptosis. To explore this potential anti-apoptotic mechanism, we inhibited calpain and proteasome activity in oridonin-induced L929 cell apoptosis, and discovered that the inducible IkappaBalpha proteolysis was partially blocked by the inhibition of either calpain or proteasome, but completely blocked by the inhibition of both. It demonstrated that calpain and proteasome were two distinct pathways participating in IkappaBalpha degradation. To further study the role of calpain in oridonin-induced L929 cell autophagy, we discovered that calpain inhibitor decreased oridonin-induced autophagy, as well as Beclin 1 activation and the conversion from LC3-I to LC3-II. Moreover, Inhibition of autophagy by 3-MA increased oridonin-induced apoptosis. In conclusion, besides suppressing apoptosis, calpain promotes autophagy in oridonin-induced L929 cell death, and inhibition of autophagy might contribute to up-regulation of apoptosis.
Cheng
Yan
Y
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Wenhua Road 103#, Shenyang 110016, China. chengyan0677@163.com
Qiu
Feng
F
Huang
Jian
J
Tashiro
Shin-Ichi
S
Onodera
Satoshi
S
Ikejima
Takashi
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002154:Calpain / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007739:L Cells; D051379:Mice; D013997:Time Factors
D004224:Diterpenes; D045786:Diterpenes, Kaurane; C011959:oridonin; D002154:Calpain