Role of Reactive Oxygen Species-Mediated Signaling in Aging

Labunskyy, Vyacheslav M.; Gladyshev, Vadim N.

doi:10.1089/ars.2012.4891

Cited by 100 publications

(77 citation statements)

References 86 publications

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“…OS plays a dualistic role in skeletal muscle: on the one hand, low levels of OS contribute to the maintenance of muscle homeostasis in different physiological conditions, e.g., physical activity [64][65][66]; on the other hand, excessive ROS production leads to alteration of skeletal muscle homeostasis and is involved in muscle damage in several pathological conditions [67][68][69]. Since neurodegenerative conditions and aging have been associated with chronically elevated levels of ROS, antioxidant treatments have been proposed or are currently in clinical trial [70][71][72].…”

Section: Discussionmentioning

confidence: 99%

HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses

et al. 2018

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Background: Denervation triggers numerous molecular responses in skeletal muscle, including the activation of catabolic pathways and oxidative stress, leading to progressive muscle atrophy. Histone deacetylase 4 (HDAC4) mediates skeletal muscle response to denervation, suggesting the use of HDAC inhibitors as a therapeutic approach to neurogenic muscle atrophy. However, the effects of HDAC4 inhibition in skeletal muscle in response to long-term denervation have not been described yet. Methods: To further study HDAC4 functions in response to denervation, we analyzed mutant mice in which HDAC4 is specifically deleted in skeletal muscle. Results: After an initial phase of resistance to neurogenic muscle atrophy, skeletal muscle with a deletion of HDAC4 lost structural integrity after 4 weeks of denervation. Deletion of HDAC4 impaired the activation of the ubiquitin-proteasome system, delayed the autophagic response, and dampened the OS response in skeletal muscle. Inhibition of the ubiquitinproteasome system or the autophagic response, if on the one hand, conferred resistance to neurogenic muscle atrophy; on the other hand, induced loss of muscle integrity and inflammation in mice lacking HDAC4 in skeletal muscle. Moreover, treatment with the antioxidant drug Trolox prevented loss of muscle integrity and inflammation in in mice lacking HDAC4 in skeletal muscle, despite the resistance to neurogenic muscle atrophy. Conclusions: These results reveal new functions of HDAC4 in mediating skeletal muscle response to denervation and lead us to propose the combined use of HDAC inhibitors and antioxidant drugs to treat neurogenic muscle atrophy.

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Section: Discussionmentioning

confidence: 99%

HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses

et al. 2018

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“…As H 2 O 2 serves as an important signaling molecule, both GPx1 deficiency and its increased activity are expected to regulate H 2 O 2 -mediated responses. According to one of the models, H 2 O 2 can directly oxidize target proteins (e.g., receptor proteins that activate downstream signaling cascades) (196). Oxidation of regulatory amino acids in such proteins can lead to alteration of their structure and augment protein function.…”

Section: Selenoprotein Functionmentioning

confidence: 99%

“…This mode of regulation is observed, for example, in tyrosine protein phosphatase 1B (300) and PTEN (194). According to the second model, GPx family proteins and other thiol-dependent peroxidases can serve as sensors of H 2 O 2 levels in the cell, which then transfer oxidizing equivalents from H 2 O 2 to target proteins (196). Support for this model was provided by a recent observation that deletion of all eight peroxidases in yeast (yeast encodes 3 GPxs and 5 peroxiredoxins) renders cells unable to sense H 2 O 2 and activate transcriptional response to oxidative stress (105).…”

Section: Selenoprotein Functionmentioning

confidence: 99%

Selenoproteins: Molecular Pathways and Physiological Roles

Labunskyy

Hatfield

Gladyshev³

2014

Physiological Reviews

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983

784

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Selenium is an essential micronutrient with important functions in human health and relevance to several pathophysiological conditions. The biological effects of selenium are largely mediated by selenium-containing proteins (selenoproteins) that are present in all three domains of life. Although selenoproteins represent diverse molecular pathways and biological functions, all these proteins contain at least one selenocysteine (Sec), a seleniumcontaining amino acid, and most serve oxidoreductase functions. Sec is cotranslationally inserted into nascent polypeptide chains in response to the UGA codon, whose normal function is to terminate translation. To decode UGA as Sec, organisms evolved the Sec insertion machinery that allows incorporation of this amino acid at specific UGA codons in a process requiring a cis-acting Sec insertion sequence (SECIS) element. Although the basic mechanisms of Sec synthesis and insertion into proteins in both prokaryotes and eukaryotes have been studied in great detail, the identity and functions of many selenoproteins remain largely unknown. In the last decade, there has been significant progress in characterizing selenoproteins and selenoproteomes and understanding their physiological functions. We discuss current knowledge about how these unique proteins perform their functions at the molecular level and highlight new insights into the roles that selenoproteins play in human health.

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“…Oxidative stress has been shown to prevail in neurodegenerative disorder like Parkinson's disease [196,197]. Furthermore, a correlation between aging and accumulation of oxidative damage has been observed [198]. It was thus posited that oxidation of VCP may play a role in the molecular physiopathology of neurodegenerative disorders, where the onset of symptoms typically comes at a later age.…”

Section: S-glutathionylationmentioning

confidence: 99%

Regulation of molecular chaperones through post-translational modifications: Decrypting the chaperone code

Cloutier

Coulombe

2013

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Molecular chaperones and their associated cofactors form a group of highly specialized proteins that orchestrate the folding and unfolding of other proteins and the assembly and disassembly of protein complexes. Chaperones are found in all cell types and organisms, and their activity must be tightly regulated to maintain normal cell function. Indeed, deregulation of protein folding and protein complex assembly is the cause of various human diseases. Here, we present the results of an extensive review of the literature revealing that the post-translational modification (PTM) of chaperones has been selected during evolution as an efficient mean to regulate the activity and specificity of these key proteins. Because the addition and reciprocal removal of chemical groups can be triggered very rapidly, this mechanism provides an efficient switch to precisely regulate the activity of chaperones on specific substrates. The large number of PTMs detected in chaperones suggests that a combinatory code is at play to regulate function, activity, localization, and substrate specificity for this group of biologically important proteins. This review surveys the core information currently available as a starting point toward the more ambitious endeavor of deciphering the "chaperone code".

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Role of Reactive Oxygen Species-Mediated Signaling in Aging

Cited by 100 publications

References 86 publications

HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses

HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses

Selenoproteins: Molecular Pathways and Physiological Roles

Regulation of molecular chaperones through post-translational modifications: Decrypting the chaperone code

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