Depression of peak force without altering calcium sensitivity by the superoxide anion in chemically skinned cardiac muscle of rat.

MacFarlane, Niall G.; Miller, D. J.

doi:10.1161/01.res.70.6.1217

Cited by 77 publications

(45 citation statements)

References 19 publications

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“…It has also been demonstrated that, while O 2 ⅐ Ϫ can depress maximum force, it has no apparent effect on the sensitivity of the contractile apparatus to Ca 2ϩ (4,39). Similar results were obtained on cardiac muscle where O 2 ⅐ Ϫ production decreased force but did not affect Ca 2ϩ sensitivity or SR function (21). On the basis of these findings, and the fact that, at or above 37°C, there is a marked loss in function of the isolated muscle (16), we hypothesized that the loss of skeletal muscle function at or above 37°C must be connected to the increase in the amount of O 2 ⅐ Ϫ produced by the mitochondria in the skeletal muscle fibers.…”

supporting

confidence: 84%

Mitochondrial superoxide production in skeletal muscle fibers of the rat and decreased fiber excitability

Poel¹,

Edwards²,

Macdonald³

et al. 2007

American Journal of Physiology-Cell Physiology

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van der Poel C, Edwards JN, Macdonald WA, Stephenson DG. Mitochondrial superoxide production in skeletal muscle fibers of the rat and decreased fiber excitability. Am J Physiol Cell Physiol 292: C1353-C1360, 2007. First published November 22, 2006; doi:10.1152/ajpcell.00469.2006.-Mammalian skeletal muscles generate marked amounts of superoxide (O2 ⅐ Ϫ ) at 37°C, but it is not well understood which is the main source of O 2 ⅐ Ϫ production in the muscle fibers and how this interferes with muscle function. To answer these questions, O 2 ⅐ Ϫ production and twitch force responses were measured at 37°C in mechanically skinned muscle fibers of rat extensor digitorum longus (EDL) muscle. In mechanically skinned fibers, the sarcolemma is removed avoiding potential sources of O 2 ⅐ Ϫ production that are not intrinsically part of the muscle fibers, such as nerve terminals, blood cells, capillaries and other blood vessels in the whole muscle. O 2 ⅐ Ϫ production was also measured in split single EDL muscle fibers, where part of the sarcolemma remained attached, and small bundles of intact isolated EDL muscle fibers at rest, in the presence and absence of modifiers of mitochondrial function. The results lead to the conclusion that mitochondrial production of O 2 ⅐ Ϫ accounts for most of the O2 ⅐ Ϫ measured intracellularly or extracellularly in skeletal muscle fibers at rest and at 37°C. Muscle fiber excitability at 37°C was greatly improved in the presence of a membrane permeant O 2 ⅐ Ϫ dismutase mimetic (Tempol), demonstrating a direct link between O 2 ⅐ Ϫ production in the mitochondria and muscle fiber performance. This implicates mitochondrial O2 ⅐ Ϫ production in the down-regulation of skeletal muscle function, thus providing a feedback pathway for communication between mitochondria and plasma membranes that is not directly related to the main function of mitochondria as the power plant of the mammalian muscle cell. excitation-contraction coupling; mechanically skinned fiber; physiological temperature NUMEROUS STUDIES HAVE REVEALED that the extracellular concentration of superoxide (O 2 ⅐ Ϫ ) markedly increases during muscle contraction and as temperature is increased above normal physiological temperatures (2,9,20,31,32, 39,41).Recently, it has been demonstrated that intracellular levels of reactive oxygen species (ROS), in particular O 2 ⅐ Ϫ , are increased as the temperature of rat diaphragm was raised from 25 to 43°C (41). This increase in intracellular O 2 ⅐ Ϫ was accompanied by an increase in extracellular O 2 ⅐ Ϫ . O 2 ⅐ Ϫ production in whole muscle tissue may arise not only from muscle fibers but also from other cellular structures such as nerve terminals, blood cells, and capillaries (38). Furthermore, in addition to mitochondria, there are a number of other sources of O 2 ⅐ Ϫ production involving 5-lipoxygenase, cyclooxygenase, xanthine oxidase, and NAD(P)H oxidase (41). Indeed, through the use of specific mitochondrial electron transport chain blockers, it has been hypothesized that the major site of intracell...

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supporting

confidence: 84%

Mitochondrial superoxide production in skeletal muscle fibers of the rat and decreased fiber excitability

Poel¹,

Edwards²,

Macdonald³

et al. 2007

American Journal of Physiology-Cell Physiology

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“…In spite of suggestions that SH oxidation of tropomyosin and/or actin in combination with myosin light chain1 (MLC1) (Hertelendi et al 2008) are potential mediators of oxidative myocardial contractile depression, it is currently difficult to clearly state that oxidation of myofilament proteins causes cardiac dysfunction, since studies have reported equivocal effects in different muscle types and even within a single muscle type. The role of oxidation of myofilament proteins in cardiac dysfunction in the heart is currently confused, as decreased Ca 2+ sensitivity has been reported (Posterino and Lamb 1996;Lamb and Posterino 2003;Hertelendi et al 2008) while others reported no changes or even increases in Ca 2+ sensitivity (MacFarlane and Miller 1992;MacFarlane and Miller 1994). Interestingly, slow twitch muscle differed from fast twitch muscle in relation to the addition of cysteine oxidants during muscle contraction (Lamb et al 1995;Lamb and Posterino 2003), suggesting that oxidative responses may be dependent on positions and differences between cysteines in fast and slow skeletal muscle.…”

Section: Impact Of Oxidative Stress On Cardiomyocyte Stiffness Sarcommentioning

confidence: 99%

A change of heart: oxidative stress in governing muscle function?

Breitkreuz

Hamdani

2015

Biophys Rev

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Redox/cysteine modification of proteins that regulate calcium cycling can affect contraction in striated muscles. Understanding the nature of these modifications would present the possibility of enhancing cardiac function through reversible cysteine modification of proteins, with potential therapeutic value in heart failure with diastolic dysfunction. Both heart failure and muscular dystrophy are characterized by abnormal redox balance and nitrosative stress. Recent evidence supports the synergistic role of oxidative stress and inflammation in the progression of heart failure with preserved ejection fraction, in concert with endothelial dysfunction and impaired nitric oxide-cyclic guanosine monophosphate-protein kinase G signalling via modification of the giant protein titin. Although antioxidant therapeutics in heart failure with diastolic dysfunction have no marked beneficial effects on the outcome of patients, it, however, remains critical to the understanding of the complex interactions of oxidative/nitrosative stress with pro-inflammatory mechanisms, metabolic dysfunction, and the redox modification of proteins characteristic of heart failure. These may highlight novel approaches to therapeutic strategies for heart failure with diastolic dysfunction. In this review, we provide an overview of oxidative stress and its effects on pathophysiological pathways. We describe the molecular mechanisms driving oxidative modification of proteins and subsequent effects on contractile function, and, finally, we discuss potential therapeutic opportunities for heart failure with diastolic dysfunction.

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“…1,3,7,9,10 Furthermore, altered myofilament responsiveness may be involved in OH-induced dysfunction. 11 The troponin complex may be a potential target, whereby radicals may interact directly with the molecules or initiate specific, possibly Ca 2ϩ -dependent, proteolytic pathways. 3,12,13 The relative contribution of these different subcellular defects to the development of acute myocardial dysfunction after OH exposure remains unresolved.…”

mentioning

confidence: 99%

Hydroxyl Radical-Induced Acute Diastolic Dysfunction Is Due to Calcium Overload via Reverse-Mode Na ⁺ -Ca ²⁺ Exchange

Zeitz

Maass²,

Nguyen³

et al. 2002

Circulation Research

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Abstract-Hydroxyl radicals (OH) are involved in the development of reperfusion injury and myocardial failure. In the acute phase of the OH-mediated diastolic dysfunction, increased intracellular Ca 2ϩ levels and alterations of myofilaments may play a role, but the relative contribution of these systems to myocardial dysfunction is unknown. Intact contracting cardiac trabeculae from rabbits were exposed to OH, resulting in an increase in diastolic force (F dia ) by 540%. Skinned fiber experiments revealed that OH-exposed preparations were sensitized for Ca 2ϩ (EC 50 : 3.27Ϯ0.24ϫ10Ϫ6 versus 2.69Ϯ0.15ϫ10 Ϫ6 mol/L; PϽ0.05), whereas maximal force development was unaltered. Western blots showed a proteolytic degradation of troponin T (TnT) with intact troponin I (TnI). Blocking of calpain I by MDL-28.170 inhibited both TnT-proteolysis and Ca 2ϩ sensitization, but failed to prevent the acute diastolic dysfunction in the intact preparation. The OH-induced diastolic dysfunction was similar in preparations with intact (540Ϯ93%) and pharmacologically blocked sarcoplasmic reticulum (539Ϯ77%), and was also similar in presence of the L-type Ca 2ϩ -channel antagonist verapamil. In sharp contrast, inhibition of the reverse-mode sodium-calcium exchange by KB-R7943 preserved diastolic function completely. Additional experiments were performed in rat myocardium; the rise in diastolic force was comparable to rabbit myocardium, but Ca 2ϩ sensitivity was unchanged and maximal force development was reduced. This was associated with a degradation of TnI, but not TnT. Electron microscopic analysis revealed that OH did not cause irreversible membrane damage. We conclude that OH-induced acute diastolic dysfunction is caused by Ca 2ϩ influx via reverse mode of the sodium-calcium exchanger. Degradation of troponins appears to be species-dependent but does not contribute to the acute diastolic dysfunction.

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Depression of peak force without altering calcium sensitivity by the superoxide anion in chemically skinned cardiac muscle of rat.

Cited by 77 publications

References 19 publications

Mitochondrial superoxide production in skeletal muscle fibers of the rat and decreased fiber excitability

Mitochondrial superoxide production in skeletal muscle fibers of the rat and decreased fiber excitability

A change of heart: oxidative stress in governing muscle function?

Hydroxyl Radical-Induced Acute Diastolic Dysfunction Is Due to Calcium Overload via Reverse-Mode Na ⁺ -Ca ²⁺ Exchange

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Depression of peak force without altering calcium sensitivity by the superoxide anion in chemically skinned cardiac muscle of rat.

Cited by 77 publications

References 19 publications

Mitochondrial superoxide production in skeletal muscle fibers of the rat and decreased fiber excitability

Mitochondrial superoxide production in skeletal muscle fibers of the rat and decreased fiber excitability

A change of heart: oxidative stress in governing muscle function?

Hydroxyl Radical-Induced Acute Diastolic Dysfunction Is Due to Calcium Overload via Reverse-Mode Na + -Ca 2+ Exchange

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Hydroxyl Radical-Induced Acute Diastolic Dysfunction Is Due to Calcium Overload via Reverse-Mode Na ⁺ -Ca ²⁺ Exchange