(R)-α-Lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues: evidence for increased cysteine requirement for GSH synthesis
Section snippets
Materials
(R)-α-lipoic acid (LA) was a gift from Asta Medica (Frankfurt, Germany). Rabbit polyclonal antibodies to GCLC (catalytic subunit) were obtained as a reference [18]. All high performance liquid chromatography (HPLC) solvents were HPLC grade reagents from Fisher Scientific (Houston, TX). All other chemicals were of reagent grade or the highest quality available from Sigma (St. Louis, MO).
Animals
Rats (Fischer 344 [F344], virgin male, outbred albino), both young (2–5 mo, N=15) and old (24–28 mo, N=15;
Age-related changes in cerebral and myocardial thiol redox state
To gauge the extent of age-related changes in thiol redox status, the GSH/GSSG ratios in brains and hearts of young and old rats were examined. The cerebral GSH/GSSG ratios declined from 28.3 ± 3.8 to 13.8 ± 0.3 with age, a significant (p<0.01) 50% loss in this important redox parameter (Table 1). Paralleling the patterns observed in the brain, myocardial GSH/GSSG ratios were also markedly lower on an age basis (18.2 ± 0.3 vs. 7.7 ± 0.8 in young compared to old rats, respectively; p<0.01; Table 1),
Discussion
Maintaining the ability to respond to oxidant challenges is critical for overall survival of organisms and for ameliorating increased risks for morbidity and mortality associated with aging. In particular, a robust and responsive GSH synthesizing capacity is needed in aging cells to protect against endogenous and exogenous oxidative insults [15], [29]. Thus, it is not surprising that the expression and activities of enzymes critical for GSH synthesis are sensitively controlled to ensure timely
Acknowledgements
This work was supported by NIH Grants RO1 AG17141A and P01 AT002034-01 to T.M.H. and RO1 ES11831-01 to RLU. This work was also supported by the Environmental Health Sciences Center, Oregon State University (ES00210). The authors thank Ms. Swapna Shenvi and Mrs. Du Heath for their expert technical assistance. We are also grateful to Stephen Lawson for careful review of the manuscript.
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