Abstract
Nitric oxide (NO), peroxynitrite, and 4-hydroxynonenal (HNE) may be involved in the pathological demise of cells via apoptosis. Apoptosis induced by these agents is inhibited by Bcl-2, suggesting the involvement of mitochondria in the death pathway. In vitro, NO, peroxynitrite and HNE can cause direct permeabilization of mitochondrial membranes, and this effect is inhibited by cyclosporin A, indicating involvement of the permeability transition pore complex (PTPC) in the permeabilization event. NO, peroxynitrite and HNE also permeabilize proteoliposomes containing the adenine nucleotide translocator (ANT), one of the key components of the PTPC, yet have no or little effects on protein-free control liposomes. ANT-dependent, NO-, peroxynitrite- or HNE-induced permeabilization is at least partially inhibited by recombinant Bcl-2 protein, as well as the antioxidants trolox and butylated hydroxytoluene. In vitro, none of the tested agents (NO, peroxynitrite, HNE, and tert-butylhydroperoxide) causes preferential carbonylation HNE adduction, or nitrotyrosylation of ANT. However, all these agents induced ANT to undergo thiol oxidation/derivatization. Peroxynitrite and HNE also caused significant lipid peroxidation, which was antagonized by butylated hydroxytoluene but not by recombinant Bcl-2. Transfection-enforced expression of vMIA, a viral apoptosis inhibitor specifically targeted to ANT, largely reduces the mitochondrial and nuclear signs of apoptosis induced by NO, peroxynitrite and HNE in intact cells. Taken together these data suggest that NO, peroxynitrite, and HNE may directly act on ANT to induce mitochondrial membrane permeabilization and apoptosis.
| Original language | English |
|---|---|
| Pages (from-to) | 4305-4316 |
| Number of pages | 12 |
| Journal | Oncogene |
| Volume | 20 |
| Issue number | 32 |
| DOIs | |
| Publication status | Published - Jul 19 2001 |
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Keywords
- Apoptosis
- Bcl-2
- Mitochondria
- Permeability transition
- vMIA
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
The adenine nucleotide translocator : A target of nitric oxide, peroxynitrite, and 4-hydroxynonenal. / Vieira, Helena L A; Belzacq, Anne Sophie; Haouzi, Delphine; Bernassola, Francesca; Cohen, Isabel; Jacotot, Etienne; Ferri, Karine F.; El Hamel, Chahrazed; Bartle, Laura M.; Melino, Gerry; Brenner, Catherine; Goldmacher, Victor; Kroemer, Guido.
In: Oncogene, Vol. 20, No. 32, 19.07.2001, p. 4305-4316.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The adenine nucleotide translocator
T2 - A target of nitric oxide, peroxynitrite, and 4-hydroxynonenal
AU - Vieira, Helena L A
AU - Belzacq, Anne Sophie
AU - Haouzi, Delphine
AU - Bernassola, Francesca
AU - Cohen, Isabel
AU - Jacotot, Etienne
AU - Ferri, Karine F.
AU - El Hamel, Chahrazed
AU - Bartle, Laura M.
AU - Melino, Gerry
AU - Brenner, Catherine
AU - Goldmacher, Victor
AU - Kroemer, Guido
PY - 2001/7/19
Y1 - 2001/7/19
N2 - Nitric oxide (NO), peroxynitrite, and 4-hydroxynonenal (HNE) may be involved in the pathological demise of cells via apoptosis. Apoptosis induced by these agents is inhibited by Bcl-2, suggesting the involvement of mitochondria in the death pathway. In vitro, NO, peroxynitrite and HNE can cause direct permeabilization of mitochondrial membranes, and this effect is inhibited by cyclosporin A, indicating involvement of the permeability transition pore complex (PTPC) in the permeabilization event. NO, peroxynitrite and HNE also permeabilize proteoliposomes containing the adenine nucleotide translocator (ANT), one of the key components of the PTPC, yet have no or little effects on protein-free control liposomes. ANT-dependent, NO-, peroxynitrite- or HNE-induced permeabilization is at least partially inhibited by recombinant Bcl-2 protein, as well as the antioxidants trolox and butylated hydroxytoluene. In vitro, none of the tested agents (NO, peroxynitrite, HNE, and tert-butylhydroperoxide) causes preferential carbonylation HNE adduction, or nitrotyrosylation of ANT. However, all these agents induced ANT to undergo thiol oxidation/derivatization. Peroxynitrite and HNE also caused significant lipid peroxidation, which was antagonized by butylated hydroxytoluene but not by recombinant Bcl-2. Transfection-enforced expression of vMIA, a viral apoptosis inhibitor specifically targeted to ANT, largely reduces the mitochondrial and nuclear signs of apoptosis induced by NO, peroxynitrite and HNE in intact cells. Taken together these data suggest that NO, peroxynitrite, and HNE may directly act on ANT to induce mitochondrial membrane permeabilization and apoptosis.
AB - Nitric oxide (NO), peroxynitrite, and 4-hydroxynonenal (HNE) may be involved in the pathological demise of cells via apoptosis. Apoptosis induced by these agents is inhibited by Bcl-2, suggesting the involvement of mitochondria in the death pathway. In vitro, NO, peroxynitrite and HNE can cause direct permeabilization of mitochondrial membranes, and this effect is inhibited by cyclosporin A, indicating involvement of the permeability transition pore complex (PTPC) in the permeabilization event. NO, peroxynitrite and HNE also permeabilize proteoliposomes containing the adenine nucleotide translocator (ANT), one of the key components of the PTPC, yet have no or little effects on protein-free control liposomes. ANT-dependent, NO-, peroxynitrite- or HNE-induced permeabilization is at least partially inhibited by recombinant Bcl-2 protein, as well as the antioxidants trolox and butylated hydroxytoluene. In vitro, none of the tested agents (NO, peroxynitrite, HNE, and tert-butylhydroperoxide) causes preferential carbonylation HNE adduction, or nitrotyrosylation of ANT. However, all these agents induced ANT to undergo thiol oxidation/derivatization. Peroxynitrite and HNE also caused significant lipid peroxidation, which was antagonized by butylated hydroxytoluene but not by recombinant Bcl-2. Transfection-enforced expression of vMIA, a viral apoptosis inhibitor specifically targeted to ANT, largely reduces the mitochondrial and nuclear signs of apoptosis induced by NO, peroxynitrite and HNE in intact cells. Taken together these data suggest that NO, peroxynitrite, and HNE may directly act on ANT to induce mitochondrial membrane permeabilization and apoptosis.
KW - Apoptosis
KW - Bcl-2
KW - Mitochondria
KW - Permeability transition
KW - vMIA
UR - http://www.scopus.com/inward/record.url?scp=0035913190&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035913190&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1204575
DO - 10.1038/sj.onc.1204575
M3 - Article
C2 - 11466611
AN - SCOPUS:0035913190
VL - 20
SP - 4305
EP - 4316
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 32
ER -