Reductive stress in striated muscle cells
- PDF / 1,513,516 Bytes
- 19 Pages / 595.276 x 790.866 pts Page_size
- 5 Downloads / 169 Views
Cellular and Molecular Life Sciences
REVIEW
Reductive stress in striated muscle cells Ilaria Bellezza1 · Francesca Riuzzi1,2 · Sara Chiappalupi1,2 · Cataldo Arcuri1 · Ileana Giambanco1 · Guglielmo Sorci1,2,3 · Rosario Donato1,2 Received: 15 November 2019 / Revised: 17 January 2020 / Accepted: 3 February 2020 © Springer Nature Switzerland AG 2020
Abstract Reductive stress is defined as a condition of sustained increase in cellular glutathione/glutathione disulfide and NADH/ NAD+ ratios. Reductive stress is emerging as an important pathophysiological event in several diseased states, being as detrimental as is oxidative stress. Occurrence of reductive stress has been documented in several cardiomyopathies and is an important pathophysiological factor particularly in coronary artery disease and myocardial infarction. Excess activation of the transcription factor, Nrf2—the master regulator of the antioxidant response—, consequent in most cases to defective autophagy, can lead to reductive stress. In addition, hyperglycemia-induced activation of the polyol pathway can lead to increased NADH/NAD+ ratio, which might translate into increased levels of hydrogen sulfide—via enhanced activity of cystathionine β-synthase—that would fuel reductive stress through inhibition of mitochondrial complex I. Reductive stress may be either a potential weapon against cancer priming tumor cells to apoptosis or a cancer’s ally promoting tumor cell proliferation and making tumor cells resistant to reactive oxygen species-inducing drugs. In non-cancer pathological states reductive stress is definitely harmful paradoxically leading to reactive oxygen species overproduction via excess NADPH oxidase 4 activity. In face of the documented occurrence of reductive stress in several heart diseases, there is much less information about the occurrence and effects of reductive stress in skeletal muscle tissue. In the present review we describe relevant results emerged from studies of reductive stress in the heart and review skeletal muscle conditions in which reductive stress has been experimentally documented and those in which reductive stress might have an as yet unrecognized pathophysiological role. Establishing whether reductive stress has a (patho)physiological role in skeletal muscle will hopefully contribute to answer the question whether antioxidant supplementation to the general population, athletes, and a large cohort of patients (e.g. heart, sarcopenic, dystrophic, myopathic, cancer, and bronco-pulmonary patients) is harmless or detrimental. Keywords Oxidative stress · Heart · Skeletal muscle · Autophagy · Hyperglycemia · Physical exercise · Antioxidant · Nrf2 Abbreviations AP-1 Activating protein 1 ARE Antioxidant response element BAG3 Bcl-2-associated athanogene-3 CBS Cystathionine β-synthase ER Endoplasmic reticulum ERO1 ER oxidoreductin 1 * Rosario Donato [email protected] 1
Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132 Perugia, Italy
2
Interuniversity
Data Loading...
