Nitric oxide donors, nitrosothiols and mitochondrial respiration inhibitors induce caspase activation by different mechanisms

We investigated to what extent different types of NO donors induce caspase activation by opening of the mitochondrial permeability transition pore (PTP) or inhibition of mitochondrial respiration. We found that nitrosothiols can directly open the PTP in isolated mitochondria and cause cytochrome c r...

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Bibliographic Details
Published in:FEBS letters 2000-02, Vol.467 (2-3), p.155-159
Main Authors: Borutaite, Vilmante, Morkuniene, Ramune, Brown, Guy C.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Caspase
Caspases - metabolism
Cytochrome c Group - metabolism
Enzyme Activation - drug effects
Enzyme Inhibitors - pharmacology
Ion Channels
Macrophage
Macrophages - drug effects
Macrophages - enzymology
Membrane Proteins - metabolism
Mitochondria, Heart - drug effects
Mitochondria, Heart - enzymology
Mitochondrial Membrane Transport Proteins
Mitochondrion
Nitric oxide
Nitric Oxide Donors - pharmacology
Nitroso Compounds - pharmacology
Rats
Sulfhydryl Compounds - pharmacology
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Summary:We investigated to what extent different types of NO donors induce caspase activation by opening of the mitochondrial permeability transition pore (PTP) or inhibition of mitochondrial respiration. We found that nitrosothiols can directly open the PTP in isolated mitochondria and cause cytochrome c release, whereas NONOate donors can not. In macrophages nitrosothiols cause caspase activation that is blocked by cyclosporin A or calcium chelation, both of which prevent PTP opening, whereas caspase activation caused by NONOates is much less sensitive to these agents. Inhibitors of mitochondrial respiration did not promote PTP opening in isolated mitochondria, and although they cause caspase activation in macrophages, this activation was slower than that caused by NO donors, and was relatively insensitive to cyclosporin and calcium chelators suggesting that PTP opening was not involved.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(00)01140-6