Cytoprotective role of mitochondrial amyloid beta peptide-binding alcohol dehydrogenase against a cytotoxic aldehyde.
Recent reports on amyloid beta peptide (A beta) binding-alcohol dehydrogenase (ABAD) have revealed the link of A beta with oxidative stress derived from mitochondria in the pathogenesis of Alzheimer's disease (AD). As a novel function of ABAD, we speculate that ABAD may detoxify aldehydes, such as 4-hydroxy-2-nonenal (4-HNE). To verify this speculation, we transfected cDNA encoding ABAD into cultured cells (HeLa and SH-SY5Y), where ABAD was localized to mitochondria. ABAD-transfectants decreased the levels of externally added 4-HNE in cultured medium as detected by TLC and became resistant against external 4-HNE. Moreover, ABAD suppressed the cytotoxic effects caused by cellular 4-HNE, which were produced through excess reactive oxygen species (ROS) by treatment with an inhibitor of mitochondrial respiration, antimycin A or by adding H(2)O(2). Catabolism of 4-HNE by ABAD was inhibited by A beta, resulting in the abolishment of the cytoprotective function by ABAD against ROS. These results propose an additional role of ABAD in neural cell death in AD: ABAD detoxifies aldehydes, such as 4-HNE derived from lipid peroxides in healthy brains, and inhibited by A beta in the development of AD.
Murakami
Yayoi
Y
Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kawasaki-city, Kanagawa-pref. 211-8533, Japan.
Ohsawa
Ikuroh
I
Kasahara
Tadashi
T
Ohta
Shigeo
S
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000447:Aldehydes / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D003603:Cytotoxins / Q000008:administration & dosage; D006367:HeLa Cells; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*
D000447:Aldehydes; D003603:Cytotoxins; D024101:Mitochondrial Proteins; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human