Bax and caspases regulate increased production of mitochondria-derived reactive species in neuronal apoptosis: LACK of A role for depletion of cytochrome c from the mitochondrial electron transport chain.
Biochem Biophys Rep
; 4: 158-168, 2015 Dec.
Article
en En
| MEDLINE
| ID: mdl-29124200
A Bax-dependent increase of reactive oxygen species (ROS) and other reactive species (RS) occurs after withdrawing NGF from mouse sympathetic neurons in cell culture. Possible mechanisms underlying the increased ROS/RS are leakage of electrons from the mitochondrial electron transport chain secondary to caspase cleavage of respiratory complexes or leakage secondary to depletion of cytochrome c from the chain. We previously demonstrated that deletion of Bax or caspase 3 from these cells reduces ROS/RS production to near baseline levels indicating a central role for both Bax and caspase 3 in generating the ROS/RS. Here we depleted cytochrome c to a similar level in neurons from wild type and bax hemizygous or knockout mice by NGF withdrawal or treatment with H2O2. Death was prevented with a caspase inhibitor that caused a partial reduction of ROS/RS levels but did not completely prevent the ROS/RS increase. ROS/RS was highest in bax wild-type cells, lowest in bax knockout cells, and at an intermediate level in the bax hemizygous cells. These and our previous findings indicate that Bax and caspase 3 are necessary for the increased ROS/RS after withdrawing NGF from these cells and that little or none of the increased ROS/RS are secondary to a depletion of cytochrome c from the electron transport chain.
Apoptosis; BAF, boc-aspartyl(OMe)-fluoromethylketone; Bax; CM-H2 DCFDA, 5-(and-6)-chloromethyl-2',7' dichlorodihydrofluorescein diacetate; Cytochrome c; FCCP, carbonyl cyanide p-trifluoromethoxyphenylhydrazone; IMM, inner mitochondrial membrane; Mitochondria; NGF; NGF, nerve growth factor; O2.-, superoxide; OMM, outer mitochondrial membrane; ROS, reactive oxygen species; RS, reactive species; Reactive Oxygen; TMRM+, tetramethylrhodamine methyl ester; Δψm,, mitochondrial membrane potential
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Biochem Biophys Rep
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Países Bajos