Antioxidants & redox signaling
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Antioxid. Redox Signal. · Jan 2019
ReviewAutophagy: A Lysosome-Dependent Process with Implications in Cellular Redox Homeostasis and Human Disease.
Autophagy, a lysosome-dependent homeostatic process inherent to cells and tissues, has emerging significance in the pathogenesis of human disease. This process enables the degradation and turnover of cytoplasmic substrates via membrane-dependent sequestration in autophagic vesicles (autophagosomes) and subsequent lysosomal delivery of cargo. Recent Advances: Selective forms of autophagy can target specific substrates (e.g., organelles, protein aggregates, and lipids) for processing. Autophagy is highly regulated by oxidative stress, including exposure to altered oxygen tension, by direct and indirect mechanisms, and contributes to inducible defenses against oxidative stress. Mitochondrial autophagy (mitophagy) plays a critical role in the oxidative stress response, through maintenance of mitochondrial integrity. ⋯ Investigations that further elucidate the complex role of autophagy in the pathogenesis of disease will facilitate targeting this pathway for therapies in specific diseases.
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Antioxid. Redox Signal. · Dec 2018
Glutathione Stimulates Vitamin D Regulatory and Glucose-Metabolism Genes, Lowers Oxidative Stress and Inflammation, and Increases 25-Hydroxy-Vitamin D Levels in Blood: A Novel Approach to Treat 25-Hydroxyvitamin D Deficiency.
25-Hydroxyvitamin D [25(OH)VD] deficiency/inadequacy is a major public health issue affecting more than 1 billion people worldwide. A convincing association exists between low levels of circulating 25(OH)VD and the poor health outcomes associated with chronic diseases. However, high supraphysiological doses of VD are needed to achieve the required 25(OH)VD levels in the blood, because many subjects respond poorly to supplementation. ⋯ Supplementation with a combination of VD and LC or GSH precursor, rather than supplementation with VD alone, is beneficial and helps achieve more successful VD supplementation. Antioxid. Redox Signal. 00, 000-000.
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Antioxid. Redox Signal. · Jul 2018
Heme Oxygenase-1 Influences Satellite Cells and Progression of Duchenne Muscular Dystrophy in Mice.
Muscle damage in Duchenne muscular dystrophy (DMD) caused by the lack of dystrophin is strongly linked to inflammation. Heme oxygenase-1 (HO-1; Hmox1) is an anti-inflammatory and cytoprotective enzyme affecting myoblast differentiation by inhibiting myomiRs. The role of HO-1 has not been so far well addressed in DMD. ⋯ In dystrophin-deficient mdx mice, expression of Hmox1 in limb skeletal muscles and diaphragm is higher than in wild-type animals, being consistently elevated from 8 up to 52 weeks, both in myofibers and inflammatory leukocytes. Accordingly, HO-1 expression is induced in muscles of DMD patients. Pharmacological inhibition of HO-1 activity or genetic ablation of Hmox1 aggravates muscle damage and inflammation in mdx mice. Double knockout animals (Hmox1-/-mdx) demonstrate impaired exercise capacity in comparison with mdx mice. Interestingly, in contrast to the effect observed in muscle fibers, in dystrophin-deficient muscle satellite cells (SCs) expression of Hmox1 is decreased, while MyoD, myogenin, and miR-206 are upregulated compared with wild-type counterparts. Mdx SCs demonstrate disturbed and enhanced differentiation, which is further intensified by Hmox1 deficiency. RNA sequencing revealed downregulation of Atf3, MafK, Foxo1, and Klf2 transcription factors, known to activate Hmox1 expression, as well as attenuation of nitric oxide-mediated cGMP-dependent signaling in mdx SCs. Accordingly, treatment with NO-donor induces Hmox1 expression and inhibits differentiation. Finally, differentiation of mdx SCs was normalized by CO, a product of HO-1 activity. Innovation and Conclusions: HO-1 is induced in DMD, and HO-1 inhibition aggravates DMD pathology. Therefore, HO-1 can be considered a therapeutic target to alleviate this disease. Antioxid. Redox Signal. 00, 000-000.
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Antioxid. Redox Signal. · Mar 2018
Mammalian Circadian Period, But Not Phase and Amplitude, Is Robust Against Redox and Metabolic Perturbations.
Circadian rhythms permeate all levels of biology to temporally regulate cell and whole-body physiology, although the cell-autonomous mechanism that confers ∼24-h periodicity is incompletely understood. Reports describing circadian oscillations of over-oxidized peroxiredoxin abundance have suggested that redox signaling plays an important role in the timekeeping mechanism. Here, we tested the functional contribution that redox state and primary metabolism make to mammalian cellular timekeeping. ⋯ Circadian flux through primary metabolism is cell autonomous, driving rhythmic NAD(P)+ redox cofactor turnover and maintaining a redox balance that is permissive for circadian gene expression cycles. Redox homeostasis and PPP flux, but not glycolysis, are necessary to maintain clock amplitude, but neither redox nor glucose metabolism determines circadian period. Furthermore, cellular rhythms are sensitive to acute changes in redox balance, at least partly through regulation of PER protein. Redox and metabolic state are, thus, both inputs and outputs, but not state variables, of cellular circadian timekeeping. Antioxid. Redox Signal. 28, 507-520.
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Antioxid. Redox Signal. · Dec 2017
Contrast-Enhanced Ultrasound for Assessing Renal Perfusion Impairment and Predicting Acute Kidney Injury to Chronic Kidney Disease Progression.
Acute kidney injury (AKI) is increasingly recognized as a major risk factor leading to progression to chronic kidney disease (CKD). However, the diagnostic tools for predicting AKI to CKD progression are particularly lacking. Here, we tested the utility of contrast-enhanced ultrasound (CEUS) for predicting progression to CKD after AKI by using both mild (20-min) and severe (45-min) bilateral renal ischemia-reperfusion injury mice. ⋯ These results indicate that CEUS enables the evaluation of renal perfusion impairment associated with CKD after ischemic AKI and may serve as a noninvasive technique for assessing AKI-CKD progression. Antioxid. Redox Signal. 27, 1397-1411.