Prostaglandin A(2) activates intrinsic apoptotic pathway by direct interaction with mitochondria in HL-60 cells
- Authors
- Lee, Sun-Young; Ahn, Ji-Hyun; Ko, Kyoung Won; Kim, Jaetaek; Jeong, Seong Whan; Kim, In-Kyung; Kim, Jin; Kim, Ho-Shik
- Issue Date
- Feb-2010
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- Apoptosis; Caspase; Cytochrome c; Mitochondria; Prostaglandin A(2)
- Citation
- PROSTAGLANDINS & OTHER LIPID MEDIATORS, v.91, no.1-2, pp 30 - 37
- Pages
- 8
- Journal Title
- PROSTAGLANDINS & OTHER LIPID MEDIATORS
- Volume
- 91
- Number
- 1-2
- Start Page
- 30
- End Page
- 37
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/22615
- DOI
- 10.1016/j.prostaglandins.2009.12.003
- ISSN
- 1098-8823
2212-196X
- Abstract
- HL-60 cells treated by prostaglandin (PG) A(2) showed characteristics of apoptosis such as accumulation of hypodiploid and annexin V positive cells, condensed and fragmented nuclei, cytochrome c (Cyt C) release from mitochondria and activation of caspase-1. -2, -3. -7 and -9. PGA(2)-induced cell death was rescued by inhibitors of caspase-9 and -3, but PGA(2)-induced Cyt C release was not prevented by caspase inhibitors. During Cyt C release by PGA(2), mitochondrial transmembrane potential was maintained and mitochondrial permeability transition pore was not formed. In addition, anti-apoptotic BCL-2 family proteins like BCL-2 and BCL-XL, and ROS scavengers including ascorbic acid and 2,2,6,6-tetramethyl-1-piperidinyloxy were not able to inhibit Cyt C release as well as apoptosis by PGA(2). Finally, it was shown that PGA(2)-induced Cyt C release in vitro from purified mitochondria in the absence of cytosolic components. Furthermore, thiol-containing compounds such as N-acetylcysteine, L-cysteine and monothioglycerol prevented Cyt C release, and hence induction of apoptosis. Taken together, these results suggest that PGA(2) activates intrinsic apoptotic pathway by directly stimulating mitochondrial outer membrane permeabilization to release Cyt C, in which thiol-reactivity of PGA(2) plays a pivotal role. (C) 2009 Elsevier Inc. All rights reserved.
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