Porphyrin Induced Calcium Release from Skeletal Muscle Sarcoplasmic Reticulum

Abramson, Jonathan J.; Milne, Stephen W.; Buck, Edmond D.; Pessah, Isaac N.

doi:10.1006/abbi.1993.1162

Cited by 28 publications

(42 citation statements)

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“…The elevated Ca 2 þ can be redistributed to mitochondria through the Ca 2 þ uniporter or to the SR through SERCA pump. Data from skeletal muscle SR fragments indicated that DOX could bind to Ryr-1 resulting in Ca 2 þ release from the SR (Abramson et al, 1988). However, we could not detect a spontaneous DOX-induced Ca 2 þ flux in the absence of a contraction-stimulating component like ATP or caffeine.…”

Section: Discussioncontrasting

confidence: 62%

“…However, we could not detect a spontaneous DOX-induced Ca 2 þ flux in the absence of a contraction-stimulating component like ATP or caffeine. The difference between these findings might be that the C2C12 myotubes are an intact cellular system, whereas Abramson et al (1988) used SR fragments. Our finding that relaxation time is especially changed in skeletal muscle suggests a reduction in Ca 2 þ re-uptake in the mitochondria or SR, leading initially to increased calcium responses and prolonged muscle relaxation times.…”

Section: Discussionmentioning

confidence: 95%

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Direct effects of doxorubicin on skeletal muscle contribute to fatigue

et al. 2009

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Chemotherapy-induced fatigue is a multidimensional symptom. Oxidative stress has been proposed as a working mechanism for anthracycline-induced cardiotoxicity. In this study, doxorubicin (DOX) was tested on skeletal muscle function. Doxorubicin induced impaired ex vivo skeletal muscle relaxation followed in time by contraction impediment, which could be explained by DOXinduced changes in Ca 2 þ responses of myotubes in vitro. The Ca 2 þ responses in skeletal muscle, however, could not be explained by oxidative stress.

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Section: Discussioncontrasting

confidence: 62%

Section: Discussionmentioning

confidence: 95%

Direct effects of doxorubicin on skeletal muscle contribute to fatigue

et al. 2009

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“…Mechanisms for doxorubicin toxicity suggested by earlier studies include: free radical generation and lipid peroxidation (49)(50)(51)(52), reactive sulfhydryl groups (53,54), binding to channel regulatory sites (25,28,31,32), or inhibited mRNA/protein synthesis (55)(56)(57)(58). The results to date have been conflicting, possibly complicated by the potential oftwo different mechanisms, one for acute toxicity and one for the late (chronic) toxicity; or by the potential of different mechanisms during therapeutic dosing versus much higher dosing; or by different mechanisms for doxorubicin toxicity in various in vitro conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, a number of studies have focused on the in vitro effects of anthracyclines on function of the pumps and channels of this subcellular membrane system. Doxorubicin induces calcium release from isolated sarcoplasmic reticulum vesicles and in skinned cardiac fibers (25)(26)(27)(28)(29)(30). ["C]-Doxorubicin binds to the calcium release channel in fractions enriched in terminal cistemae (31,32).…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin cardiomyopathy is associated with a decrease in calcium release channel of the sarcoplasmic reticulum in a chronic rabbit model.

Dodd¹,

Atkinson²,

Olson³

et al. 1993

J. Clin. Invest.

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Doxorubicin is a highly effective cancer chemotherapeutic agent that produces a dose-dependent cardiomyopathy that limits its clinical usefulness. Clinical and animal studies ofmorphological changes during the early stages of doxorubicin-induced cardiomyopathy have suggested that the sarcoplasmic reticulum, the intracellular membrane system responsible for myoplasmic calcium regulation in adult mammalian heart, may be the early target of doxorubicin. To detect changes in the calcium pump protein or the calcium release channel (ryanodine receptor) of the sarcoplasmic reticulum during chronic doxorubicin treatment, rabbits were treated with intravenous doxorubicin (1 mg/kg) twice weekly for 12 to 18 doses. Pair-fed controls received intravenous normal saline. The severity ofcardiomyopathy was scored by light and electron microscopy of left ventricular papillary muscles. Developed tension was measured in isolated atrial strips. In subcellular fractions from heart, I3Hjryanodine binding was decreased in doxorubicin-treated rabbits (0.33±0.03 pmol/mg) compared with control rabbits (0.66±0.02 pmol/mg, P < 0.0001). The magnitude of the decrease in I3Hjryanodine binding correlated with both the severity of the cardiomyopathy graded by pathology score (light and electron microscopy) and the decrease in developed tension in isolated atrial strips. B. for [3Hlryanodine binding and the amount of immunoreactive ryanodine receptor by Western blot analysis using sequence-specific antibody were both decreased, consistent with a decrease in the amount of calcium release channel of sarcoplasmic reticulum in doxorubicin-treated rabbits. In contrast, there was no decrease in the amount or the activity of the calcium pump protein of the sarcoplasmic reticulum in doxorubicin-treated rabbits. Doxorubicin treatment did not decrease [3H I ryanodine binding or the amount ofimmunoreactive calcium release channel of sarcoplasmic reticulum in skeletal muscle. Since the sarcoplasmic reticulum regulates muscle contraction by the cyclic uptake and release of a large internal calcium pool, altered function of the calcium release channel could lead to the abnormalities ofcontraction and relaxation observed in the doxorubicin cardiomyopathy. (J. Clin.A portion of this paper has been presented in abstract form ( 1991.Biophys. J. 59: lOla).

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“…1 and 2b), optimal Ca 2+ -releasing concentrations of Clof or other types of CICR activators (caffeine or adenine nucleotides) are much higher (>several hundred m M). Thus, Cer might be classified as a type of activator that can cause Ca 2+ release at relatively low concentrations, as is 4-chloro-m-cresol (19,20) or doxorubicin (21,22).…”

Section: +mentioning

confidence: 99%

Ca2+-Releasing Effect of Cerivastatin on the Sarcoplasmic Reticulum of Mouse and Rat Skeletal Muscle Fibers

et al. 2003

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Abstract. We analyzed the effect of HMG-CoA reductase inhibitors on Ca 2+ release from the sarcoplasmic reticulum (SR) using chemically skinned skeletal muscle fibers from the mouse and the rat. Cerivastatin (>20 m M) released Ca 2+ from the SR, while pravastatin showed only a little effect. The rates of Ca 2+ release were increased by cerivastatin at all Ca 2+ concentrations tested. Cerivastatin-induced Ca 2+ release in the presence of Ca 2+ was affected by adenosine monophosphate, Mg 2+, and procaine in essentially the same way as for caffeine-induced Ca 2+release. The Ca 2+-uptake capacity of the SR was reduced after co-treatment with ryanodine and cerivastatin at pCa 6.0 to a much greater extent than with ryanodine alone. Thus, cerivastatininduced Ca 2+ release in the presence of Ca 2+ must be a result of the activation of the Ca 2+-induced Ca 2+ release (CICR) mechanism of the ryanodine receptor. However, even when CICR was maximally inhibited by Mg 2+ and procaine, or in the practical absence of Ca 2+ (pCa >8), cerivastatin still caused Ca 2+ release. These results indicate that cerivastatin causes Ca 2+ release also by activating some other mechanism(s) in addition to the activation of CICR. Either or both of these effects might be related to its adverse effect, rhabdomyolysis.

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Porphyrin Induced Calcium Release from Skeletal Muscle Sarcoplasmic Reticulum

Cited by 28 publications

References 0 publications

Direct effects of doxorubicin on skeletal muscle contribute to fatigue

Direct effects of doxorubicin on skeletal muscle contribute to fatigue

Doxorubicin cardiomyopathy is associated with a decrease in calcium release channel of the sarcoplasmic reticulum in a chronic rabbit model.

Ca2+-Releasing Effect of Cerivastatin on the Sarcoplasmic Reticulum of Mouse and Rat Skeletal Muscle Fibers

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