The role of toll‐like receptor 4 in mitochondrial function and reactive oxygen species (ROS) production in skeletal muscle

SummaryThe hypoxia-inducible transcription factor HIF-1 mediates upregulation of plasminogen activator inhibitor-1 (PAI-1) expression under hypoxia. Reactive oxygen species (ROS) have also been implicated in PAI-1 gene expression. However, the role of ROS in HIF-1-mediated regulation of PAI-1 is not clear. We therefore investigated the role of the GTPase Rac1 which modulates ROS production in the pathway leading to HIF-1 and PAI-1 induction.Overexpression of constitutively activated (RacG12V) or dominant-negative (RacT17N) Rac1 increased or decreased, respectively, ROS production. In RacG12V-expressing cells, PAI-1 mRNA levels as well as HIF-1α nuclear presence were reduced under normoxia and hypoxia whereas expression of RacT17N resulted in opposite effects. Treatment with the antioxidant pyrrolidinedithiocarbamate or coexpression of the redox factor-1 restored HIF-1 and PAI-1 promoter activity in RacG12V-cells. In contrast, NFκB activation was enhanced in RacG12V-cells, but abolished by RacT17N. Thus, these findings suggest a mechanism explaining modified fibrinolysis and tissue remodeling in an oxidized environment.

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Effects of acute hyperinsulinemia on skeletal muscle mitochondrial function, reactive oxygen species production, and metabolism in premenopausal women

Metabolism ◽

10.1016/j.metabol.2017.08.004 ◽

2017 ◽

Vol 77 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Jonathan L. Warren ◽

Sule Bulur ◽

Fernando Ovalle ◽

Samuel T. Windham ◽

Barbara A. Gower ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Skeletal Muscle ◽

Mitochondrial Function ◽

Reactive Oxygen Species Production ◽

Reactive Oxygen ◽

Premenopausal Women ◽

Oxygen Species ◽

Species Production

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Graphene and graphene oxide induce ROS production in human HaCaT skin keratinocytes: the role of xanthine oxidase and NADH dehydrogenase

Nanoscale ◽

10.1039/c8nr02933d ◽

2018 ◽

Vol 10 (25) ◽

pp. 11820-11830 ◽

Cited By ~ 37

Author(s):

Marco Pelin ◽

Laura Fusco ◽

Cristina Martín ◽

Silvio Sosa ◽

Javier Frontiñán-Rubio ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Graphene Oxide ◽

Xanthine Oxidase ◽

Nadh Dehydrogenase ◽

Reactive Oxygen ◽

Ros Production ◽

Oxygen Species ◽

Mitochondrial Depolarization ◽

Skin Keratinocytes

Graphene based nanomaterials induce a reactive oxygen species-mediated mitochondrial depolarization, caused by the activation of NADH dehydrogenase and xanthine oxidase.

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Reduced Mitochondrial Content, Elevated Reactive Oxygen Species, and Modulation by Denervation in Skeletal Muscle of Prefrail or Frail Elderly Women

The Journals of Gerontology Series A ◽

10.1093/gerona/glz066 ◽

2019 ◽

Vol 74 (12) ◽

pp. 1887-1895 ◽

Cited By ~ 6

Author(s):

Vita Sonjak ◽

Kathryn J Jacob ◽

Sally Spendiff ◽

Madhusudanarao Vuda ◽

Anna Perez ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Skeletal Muscle ◽

Mitochondrial Function ◽

Frail Elderly ◽

Elderly Women ◽

Reactive Oxygen ◽

Oxygen Species ◽

Respiratory Capacity ◽

Species Response ◽

Mitochondrial Impairment

Abstract Denervation and mitochondrial impairment are implicated in age-related skeletal muscle atrophy and may play a role in physical frailty. We recently showed that denervation modulates muscle mitochondrial function in octogenarian men, but this has not been examined in elderly women. On this basis, we tested the hypothesis that denervation plays a modulating role in mitochondrial impairment in skeletal muscle from prefrail or frail elderly (FE) women. Mitochondrial respiratory capacity and reactive oxygen species emission were examined in permeabilized myofibers obtained from vastus lateralis muscle biopsies from FE and young inactive women. Muscle respiratory capacity was reduced in proportion to a reduction in a mitochondrial marker protein in FE, and mitochondrial reactive oxygen species emission was elevated in FE versus young inactive group. Consistent with a significant accumulation of neural cell adhesion molecule-positive muscle fibers in FE (indicative of denervation), a 50% reduction in reactive oxygen species production after pharmacologically inhibiting the denervation-mediated reactive oxygen species response in FE women suggests a significant modulation of mitochondrial function by denervation. In conclusion, our data support the hypothesis that denervation plays a modulating role in skeletal muscle mitochondrial function in FE women, suggesting therapeutic strategies in advanced age should focus on the causes and treatment of denervation.

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Hypoxia-induced reactive oxygen species formation in skeletal muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.01298.2006 ◽

2007 ◽

Vol 102 (6) ◽

pp. 2379-2388 ◽

Cited By ~ 213

Author(s):

Thomas L. Clanton

Keyword(s):

Reactive Oxygen Species ◽

Skeletal Muscle ◽

Molecular Mechanisms ◽

Cell Injury ◽

Cell Function ◽

Contractile Activity ◽

Reactive Oxygen ◽

Hypoxic Exposure ◽

Ros Production ◽

Oxygen Species

The existence of hypoxia-induced reactive oxygen species (ROS) production remains controversial. However, numerous observations with a variety of methods and in many cells and tissue types are supportive of this idea. Skeletal muscle appears to behave much like heart in that in the early stages of hypoxia there is a transient elevation in ROS, whereas in chronic exposure to very severe hypoxia there is evidence of ongoing oxidative stress. Important remaining questions that are addressed in this review include the following. Are there levels of Po2 in skeletal muscle, typical of physiological or mildly pathophysiological conditions, that are low enough to induce significant ROS production? Does the ROS associated with muscle contractile activity reflect imbalances in oxygen uptake and demand that drive the cell to a more reduced state? What are the possible molecular mechanisms by which ROS may be elevated in hypoxic skeletal muscle? Is the production of ROS in hypoxia of physiological significance, both with respect to cell signaling pathways promoting cell function and with respect to damaging effects of long-term exposure? Discussion of these and other topics leads to general conclusions that hypoxia-induced ROS may be a normal physiological response to imbalance in oxygen supply and demand or environmental stress and may play a yet undefined role in normal response mechanisms to these stimuli. However, in chronic and extreme hypoxic exposure, muscles may fail to maintain a normal redox homeostasis, resulting in cell injury or dysfunction.

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Ascorbic acid improves mitochondrial function in liver of arsenic-treated rat

Toxicology and Industrial Health ◽

10.1177/0748233710365694 ◽

2010 ◽

Vol 26 (5) ◽

pp. 265-272 ◽

Cited By ~ 16

Author(s):

Sohini Singh ◽

Suresh Vir Singh Rana

Keyword(s):

Reactive Oxygen Species ◽

Ascorbic Acid ◽

Mitochondrial Function ◽

Caspase 3 ◽

Succinic Dehydrogenase ◽

Reactive Oxygen ◽

Ultrastructural Changes ◽

Arsenic Toxicity ◽

Oxygen Species

Arsenic is an ubiquitous and well-documented carcinogenic metalloid. The most common source of arsenic is drinking water. The mechanism of arsenic toxicity in a cell has historically been centered around its inhibitory effects on cellular respiration and mitochondrial injury. Ascorbic acid, a low molecular weight, water-soluble antioxidant, improves the reduced glutathione (GSH) status by recycling oxidized glutathione. Ascorbic acid can improve mitochondrial function by improving the thiol status; thereby preventing reactive oxygen species— mediated damage to liver as well as kidney. Ascorbic acid has been shown to protect membrane and other cellular compartments by regenerating vitamin E. Therefore, ascorbic acid seems to be a suitable protective factor against arsenic toxicity. Present reports describe the effect of ascorbic acid on oxidative phosphorylation, adenosine triphosphatase (ATPase), succinic dehydrogenase, caspase-3 and apoptosis in the liver of rats treated with arsenic trioxide (AsIII). Ultrastructural changes in the mitochondria have also been reported. We show that cotreatments with ascorbic acid and AsIII improve mitochondrial structure and function. We attribute these improvements mainly to antioxidative role of ascorbic acid. Apoptosis was restricted due to caspase-3 inhibition. Ascorbic acid could protect DNA from the attack of reactive oxygen species generated by AsIII. Consequently its events led to improved ADP:O ratio, normalized ATPase activity and restored the activity of succinic dehydrogenase. Overall, results support the protective role of ascorbic acid against As III-induced liver injury.

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Spermatic mitochondria: role in oxidative homeostasis, sperm function and possible tools for their assessment

Zygote ◽

10.1017/s0967199418000242 ◽

2018 ◽

Vol 26 (4) ◽

pp. 251-260 ◽

Cited By ~ 12

Author(s):

João Diego de Agostini Losano ◽

Daniel de Souza Ramos Angrimani ◽

Roberta Ferreira Leite ◽

Bárbara do Carmo Simões da Silva ◽

Valquíria Hyppolito Barnabe ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Mitochondrial Function ◽

Reactive Oxygen ◽

Sperm Function ◽

Oxygen Species ◽

Functional Dynamics ◽

Fertilization Capacity ◽

Oxidative Homeostasis

SummaryDespite sperm mitochondrial relevance to the fertilization capacity, the processes involved in the production of ATP and functional dynamics of sperm mitochondria are not fully understood. One of these processes is the paradox involved between function and formation of reactive oxygen species performed by the organelle. Therefore, this review aimed to provide data on the role of sperm mitochondria in oxidative homeostasis and functionality as well the tools to assess sperm mitochondrial function.

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