| 12890888 |
Kitamura Y, Miyamura A, Takata K, Inden M, Tsuchiya D, Nakamura K, Taniguchi T: Possible involvement of both endoplasmic reticulum-and mitochondria-dependent pathways in thapsigargin-induced apoptosis in human neuroblastoma SH-SY5Y cells. J Pharmacol Sci. 2003 Jul;92(3):228-36.
Recently, it has been shown that endoplasmic reticulum (ER) stress causes apoptosis. However, the mechanism of the ER stress-dependent pathway is not fully understood. In human neuroblastoma SH-SY5Y cells, we detected a caspase-12-like protein that has a molecular mass (approximately 60 kDa) similar to that of mouse caspase-12. Thapsigargin, an inhibitor of ER-associated Ca (2+)-ATPase, induced the degradation of caspase-12-like protein. In addition, the degradation of caspases-9 and -3, cleavage of poly (ADP-ribose) polymerase, DNA fragmentation, and cell death were also observed. Pretreatment with phorbol-12-myristate-13-acetate, which induces the expression of antiapoptotic Bcl-2, inhibited thapsigargin-induced degradation of caspases-9 and -3, but not caspase-12-like protein degradation. A caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OCH (3))-CH (2) F, inhibited the degradation of caspase-12-like protein, but not that of caspases-9 and -3. These results suggest that thapsigargin may induce the activation of both ER- and mitochondria-dependent pathways in human SH-SY5Y cells. |
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