Glutathione peroxidase enzyme activity in aging.
ABSTRACT It is hypothesized that free radical damage contributes to aging. Age-related decline in activity of the antioxidant enzyme glutathione peroxidase (GPx) may contribute to increased free radicals. We hypothesized that GPx activity decreases with age in a population of older women with disability.
Whole blood GPx activity was measured in baseline stored samples from participants in the Women's Health and Aging Study I, a cohort of disabled community-dwelling older women. Linear regression was used to determine cross-sectional associations between GPx activity and age, adjusting for hemoglobin, coronary disease, diabetes, selenium, and body mass index.
Six hundred one participants had complete demographic, disease, and laboratory information. An inverse association was observed between GPx and age (regression coefficient = -2.9, p <.001), indicating that for each 1-year increase in age, GPx activity decreased by 2.9 micromol/min/L. This finding remained significant after adjustment for hemoglobin, coronary disease, diabetes, and selenium, but not after adjustment for body mass index and weight loss.
This is the first study to examine the association between age and GPx activity in an older adult cohort with disability and chronic disease. These findings suggest that, after age 65, GPx activity declines with age in older women with disability. This decline does not appear to be related to diseases that have been previously reported to alter GPx activity. Longitudinal examination of GPx activity and other antioxidant enzymes in diverse populations of older adults will provide additional insight into age- and disease-related changes in these systems.
Full-textDOI: · Available from: Sean Leng, May 29, 2015
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ABSTRACT: Reports from Alzheimer's disease (AD) biomarker work have shown a strong link between oxidative stress and AD neuropathology. The nonenzymatic antioxidant, glutathione (GSH), plays a crucial role in defense against reactive oxygen species and maintenance of GSH redox homeostasis. In particular, our previous studies on GSH redox imbalance have implicated oxidative stress induced by excessive reactive oxygen species as a major mediator of AD-like events, with the presence of S-glutathionylated proteins (Pr-SSG) appearing prior to overt AD neuropathology. Furthermore, evidence has demonstrated that oxidative stress may be associated with dysfunction of the hypothalamic-pituitary-adrenal axis, leading to activation of inflammatory pathways and increased production of corticotropin-releasing factor (CRF). Therefore, to investigate whether oxidative insults can be attenuated by reduction of central CRF signaling, we administered the type-1 CRF receptor (CRFR1) selective antagonist, R121919, to AD-transgenic mice beginning in the preclinical/prepathologic period (30-day-old) for 150 days, a timepoint where behavioral impairments and pathologic progression should be measureable. Our results indicate that R121919 treatment can significantly reduce Pr-SSG levels and increase glutathione peroxide activity, suggesting that interference of CRFR1 signaling may be useful as a preventative therapy for combating oxidative stress in AD.Journal of Alzheimer's disease: JAD 02/2015; DOI:10.3233/JAD-141722 · 3.61 Impact Factor
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ABSTRACT: Low molecular weight peptide (LMWP) was prepared from clam Paphia undulate and its antiaging effect on D-galactose-induced acute aging in rats, aged Kunming mice, ultraviolet-exposed rats, and thermally injured rats was investigated. P. undulate flesh was homogenized and digested using papain under optimal conditions, then subjected to Sephadex G-25 chromatography to isolate the LMWP. Administration of LMWP significantly reversed D-galactose-induced oxidative stress by increasing the activities of glutathione peroxidase (GPx) and catalase (CAT), and by decreasing the level of malondialdehyde (MDA). This process was accompanied by increased collagen synthesis. The LMWP prevented photoaging and promoted dermis recovery and remission of elastic fiber hyperplasia. Furthermore, treatment with the LMWP helped to regenerate elastic fibers and the collagen network, increased superoxide dismutase (SOD) in the serum and significantly decreased MDA. Thermal scald-induced inflammation and edema were also relieved by the LWMP, while wound healing in skin was promoted. These results suggest that the LMWP from P. undulate could serve as a new antiaging substance in cosmetics.Chinese Journal of Oceanology and Limnology 05/2013; 31(3). DOI:10.1007/s00343-013-2222-z · 0.68 Impact Factor
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ABSTRACT: Rationale: Protein phosphatase 2A (PP2A) is a primary serine-threonine phosphatase that modulates inflammatory responses in asthma and COPD. Despite its importance, the mechanisms that regulate lung PP2A activity remain to be determined. The redox-sensitive enzyme protein tyrosine phosphatase 1B (PTP1B) activates PP2A by dephosphorylating the catalytic subunit of the protein at tyrosine 307. Objectives: This study aimed to identify how the interaction between the intracellular antioxidant glutathione peroxidase-1 (GPx-1) and PTP1B impacted on lung PP2A activity and airway inflammation. Measurements and Main Results: Studies using gene silencing techniques in mouse lung or human small airway epithelial (SAE) cells determined that knocking down PTP1B expression blocked GPx-1's activation of PP2A and negated the anti-inflammatory effects of GPx-1 protein in the lung. Similarly, the expression of human GPx-1 in transgenic mice significantly increased PP2A and PTP1B activities and prevented chronic cigarette smoke-induced airway inflammation and alveolar destruction. GPx-1 knockout mice, however, exhibited an exaggerated emphysema phenotype, correlating with a non-responsive PP2A pathway. Importantly, GPx-1-PTP1B-PP2A signaling becomes inactivated in advanced lung diseases. Indeed, PTP1B protein was oxidized in the lungs of advanced emphysema subjects and, unlike healthy lung epithelial cells, cigarette smoke did not increase GPx-1 or PTP1B activity within epithelial cells isolated from COPD subjects. Conclusions: These findings establish that the GPx-1-PTP1B-PP2A axis plays a critical role in countering the inflammatory and proteolytic responses that result in lung tissue destruction in response to cigarette smoke exposure.American Journal of Respiratory Cell and Molecular Biology 04/2013; DOI:10.1165/rcmb.2013-0026OC · 4.11 Impact Factor