Prostaglandin A2 activates intrinsic apoptotic pathway by direct interaction with mitochondria in HL-60 cells

Sun Young Lee; Ji Hyun Ahn; Kyoung Won Ko; Jaetaek Kim; Seong Whan Jeong; In Kyung Kim; Jin Kim; Ho Shik Kim

doi:10.1016/j.prostaglandins.2009.12.003

Prostaglandin A₂ activates intrinsic apoptotic pathway by direct interaction with mitochondria in HL-60 cells

Sun Young Lee, Ji Hyun Ahn, Kyoung Won Ko, Jaetaek Kim, Seong Whan Jeong, In Kyung Kim, Jin Kim, Ho Shik Kim

Department of Biochemistry

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

HL-60 cells treated by prostaglandin (PG) A₂ 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. PGA₂-induced cell death was rescued by inhibitors of caspase-9 and -3, but PGA₂-induced Cyt C release was not prevented by caspase inhibitors. During Cyt C release by PGA₂, 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 PGA₂. Finally, it was shown that PGA₂-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 PGA₂ activates intrinsic apoptotic pathway by directly stimulating mitochondrial outer membrane permeabilization to release Cyt C, in which thiol-reactivity of PGA₂ plays a pivotal role.

Original language	English
Pages (from-to)	30-37
Number of pages	8
Journal	Prostaglandins and Other Lipid Mediators
Volume	91
Issue number	1-2
DOIs	https://doi.org/10.1016/j.prostaglandins.2009.12.003
State	Published - Feb 2010

Bibliographical note

Funding Information:
We thank Professor Marco Colombini at University of Maryland for advice and helpful discussion and Professor Seon-Yong Jeong at Ajou University for critical review. We also thank Professor Jeong-Hwa Lee for kindly providing Flag-BCL-2 and Flag-BCL-XL expressing plasmids and Hong-Lim Kim for his technical assistance for electron microscopic examination. This work was supported by the Catholic Medical Center Research Foundation made in the program year of 2006 and by the Korea Science and Engineering Foundation (KOSEF) through the MRC for Cell Death Disease Research Center at The Catholic University of Korea ( R13–2002-005–01003-0 ).

Keywords

Apoptosis
Caspase
Cytochrome c
Mitochondria
Prostaglandin A

Access to Document

10.1016/j.prostaglandins.2009.12.003

Cite this

@article{8d72c674f400491da695625914e0712a,

title = "Prostaglandin A2 activates intrinsic apoptotic pathway by direct interaction with mitochondria in HL-60 cells",

abstract = "HL-60 cells treated by prostaglandin (PG) A2 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. PGA2-induced cell death was rescued by inhibitors of caspase-9 and -3, but PGA2-induced Cyt C release was not prevented by caspase inhibitors. During Cyt C release by PGA2, 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 PGA2. Finally, it was shown that PGA2-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 PGA2 activates intrinsic apoptotic pathway by directly stimulating mitochondrial outer membrane permeabilization to release Cyt C, in which thiol-reactivity of PGA2 plays a pivotal role.",

keywords = "Apoptosis, Caspase, Cytochrome c, Mitochondria, Prostaglandin A",

author = "Lee, {Sun Young} and Ahn, {Ji Hyun} and Ko, {Kyoung Won} and Jaetaek Kim and Jeong, {Seong Whan} and Kim, {In Kyung} and Jin Kim and Kim, {Ho Shik}",

note = "Funding Information: We thank Professor Marco Colombini at University of Maryland for advice and helpful discussion and Professor Seon-Yong Jeong at Ajou University for critical review. We also thank Professor Jeong-Hwa Lee for kindly providing Flag-BCL-2 and Flag-BCL-XL expressing plasmids and Hong-Lim Kim for his technical assistance for electron microscopic examination. This work was supported by the Catholic Medical Center Research Foundation made in the program year of 2006 and by the Korea Science and Engineering Foundation (KOSEF) through the MRC for Cell Death Disease Research Center at The Catholic University of Korea ( R13–2002-005–01003-0 ). ",

year = "2010",

month = feb,

doi = "10.1016/j.prostaglandins.2009.12.003",

language = "English",

volume = "91",

pages = "30--37",

journal = "Prostaglandins and Other Lipid Mediators",

issn = "1098-8823",

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T1 - Prostaglandin A2 activates intrinsic apoptotic pathway by direct interaction with mitochondria in HL-60 cells

AU - Lee, Sun Young

AU - Ahn, Ji Hyun

AU - Ko, Kyoung Won

AU - Kim, Jaetaek

AU - Jeong, Seong Whan

AU - Kim, In Kyung

AU - Kim, Jin

AU - Kim, Ho Shik

N1 - Funding Information: We thank Professor Marco Colombini at University of Maryland for advice and helpful discussion and Professor Seon-Yong Jeong at Ajou University for critical review. We also thank Professor Jeong-Hwa Lee for kindly providing Flag-BCL-2 and Flag-BCL-XL expressing plasmids and Hong-Lim Kim for his technical assistance for electron microscopic examination. This work was supported by the Catholic Medical Center Research Foundation made in the program year of 2006 and by the Korea Science and Engineering Foundation (KOSEF) through the MRC for Cell Death Disease Research Center at The Catholic University of Korea ( R13–2002-005–01003-0 ).

PY - 2010/2

Y1 - 2010/2

N2 - HL-60 cells treated by prostaglandin (PG) A2 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. PGA2-induced cell death was rescued by inhibitors of caspase-9 and -3, but PGA2-induced Cyt C release was not prevented by caspase inhibitors. During Cyt C release by PGA2, 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 PGA2. Finally, it was shown that PGA2-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 PGA2 activates intrinsic apoptotic pathway by directly stimulating mitochondrial outer membrane permeabilization to release Cyt C, in which thiol-reactivity of PGA2 plays a pivotal role.

AB - HL-60 cells treated by prostaglandin (PG) A2 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. PGA2-induced cell death was rescued by inhibitors of caspase-9 and -3, but PGA2-induced Cyt C release was not prevented by caspase inhibitors. During Cyt C release by PGA2, 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 PGA2. Finally, it was shown that PGA2-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 PGA2 activates intrinsic apoptotic pathway by directly stimulating mitochondrial outer membrane permeabilization to release Cyt C, in which thiol-reactivity of PGA2 plays a pivotal role.

KW - Apoptosis

KW - Caspase

KW - Cytochrome c

KW - Mitochondria

KW - Prostaglandin A

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