Development of a peptide antibody specific to human glutathione S-transferase alpha 4-4 (hGSTA4-4) reveals preferential localization in human liver mitochondria.

Abstract:

:The reactive cellular products generated during the peroxidation of membrane lipids have been implicated as causative agents in a variety of degenerative diseases and aging. In particular, 4-hydroxynon-2-enal (4HNE) is among the most of the produced during lipid peroxidation. In humans and rodent species, the alpha 4 subclass of glutathione S-transferases (mGSTA4-4, rGSTA4-4, hGST-5.8, and hGSTA4-4) exhibits uniquely high glutathione conjugation activity toward 4HNE and other hydroxyalkenals. In human liver, hGSTA4-4-mediated 4HNE conjugation appears to represent the high-affinity pathway for 4HNE detoxification. In the present study, a highly specific polyclonal antibody was developed against hGSTA4-4. Western blotting analysis of human liver subcellular fractions as well as N-terminal sequencing revealed that hGSTA4-4 was localized to mitochondrial fractions, but was not detected in cytosolic fractions. Our results provide evidence that in adult liver, hGSTA4-4 is specifically targeted to the mitochondrion to the apparent exclusion of the cytosol. Targeting of hGSTA4-4 to the mitochondrion holds implications for degenerative diseases associated with oxidative stress that arise from aerobic respiration.

journal_name

Arch Biochem Biophys

authors

Gardner JL,Gallagher EP

doi

10.1006/abbi.2001.2352

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

19-27

issue

1

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(01)92352-5

journal_volume

390

pub_type

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