GSTA4
Glutathione S-transferase A4 (EC 2.5.1.18) (GST class-alpha member 4) (Glutathione S-transferase A4-4)
Publications[править]
It is not known whether aging alters the enzymatic reactive aldehyde- and lipid hydroperoxide-detoxifying capacity of the human arterial tissue favoring vascular oxidative stress. To address this issue, we studied the specific enzymatic activities of class 1, 2 and 3 aldehyde dehydrogenase (ALDH1, ALDH2 and ALDH3), glutathione S‑transferase (isozyme A4-4, GSTA4-4) and aldose reductase (AR), namely the major reactive aldehyde-scavenging enzymes, together with the activity of the lipid hydroperoxide-removing enzyme glutathione peroxidase (GSH-Px), in superior thyroid arteries (STA) specimens obtained in the thyroid surgery setting in aged subjects (age 72.3 ± 3.6 years) and young adult controls (age 31.9 ± 3.5 years). Vascular lipid peroxidation was also studied by assessing in STA fluorescent damage products of lipid peroxidation (FDPL), which reflect oxidant-induced 4‑hydroxynonenal and lipid hydroperoxide formation. Remarkably, the activities of ALDH1, ALDH2, ALDH3, GSTA4-4, AR and GSH-Px were significantly lower, and FDPL levels higher, in the arterial tissue of the aged subjects than in that of the young adult controls. Moreover, the enzymatic activities were inversely and significantly correlated with the levels of FDPL in the arterial tissue of both the aged and young subjects, highlighting their vascular antioxidant/antilipoperoxidative role in vivo. Thus, aging impairs the enzymatic reactive aldehyde-detoxifying capacity and GSH-Px activity of the human arterial tissue eventually favoring vascular oxidative stress.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Aldehyde Dehydrogenase
- Aldehyde Reductase
- Arteries
- Case-Control Studies
- Female
- Glutathione Peroxidase
- Glutathione Transferase
- Humans
- Lipid Peroxidation
- Male
- Oxidative Stress
Keywords
- Aging
- Aldehyde dehydrogenase
- Aldose reductase
- Glutathione S‑transferase
- Glutathione peroxidase
- Lipid peroxidation
- Oxidative stress
- Reactive aldehydes
Glutathione S-transferases (GSTs) are phase-II metabolic enzymes playing important roles in drug metabolism, anti-oxidative stress and anti-aging. Age is a key factor influencing GSTs expression. Thus, age-related changes of 10 GSTs were examined. Livers from male Sprague-Dawley rats at fetus (-2 d), neonates (1, 7, 14 and 21 d), puberty (28 and 35 d), adulthood (60 and 180 d), and aging (540 and 800 d), were collected and subjected to qPCR analysis. Liver proteins from 14, 28, 60, 180, 540 and 800 d were also extracted for selected protein analysis by Western-blot. The expression of GSTA1 and GSTP1 increased over the life span and the expression of GSTA4, GSTO1 and GSTZ1 gradually increased until adulthood, and slightly decreased at 800 days. The expression of GSTM1, GSTM3, GSTT1, GSTT2 and GSTK1 gradually increased until adulthood, but significantly decreased during aging of 540 and 800 days. There is a small peak at 7-14 d for GSTA1, GSTP1 and GSTZ1. The protein expression of GSTA1, GSTM1 and GSTP1 followed the trend of mRNA changes. This study characterized three expression patterns of 10 GSTs during development and aging in rat liver, adding to our understanding of anti-aging role of GSTs.
MeSH Terms
- Aging
- Animals
- Glutathione S-Transferase pi
- Glutathione Transferase
- Isoenzymes
- Liver
- Male
- Rats
- Rats, Sprague-Dawley
Keywords
- Ontogeny
- aging
- glutathione S-transferases
- rat liver