Effects of cyclosporin A on contractile activity and cytoskeleton in chick embryo cardiomyocytes

Kołcz, Jacek; Drukała, Justyna; Jurkiewicz, Anna; Pfitzner, Roman; Garlicki, M; Czyż, Jarosław; Korohoda, W

doi:10.1139/bcb-77-2-133

Cited by 3 publications

(2 citation statements)

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“…The further increase in the frequency of Ca# + oscillations induced by CsA ( Figure 7A) and FK506 ( Figure 7B) is likely to be coupled to the increased tendency of the Ca# + -release channel. This result is consistent with the increased contractility of cardiomyoctes by CsA or FK506 [43,44]. Taken together, these data suggest that inhibition of the endogenous phosphatase activity of calcineurin by calcineurin inhibitors leads to a higher probability of Ca# +release channel openings.…”

Section: Discussionsupporting

confidence: 85%

Calcineurin regulates ryanodine receptor/Ca2+-release channels in rat heart

et al. 2000

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The present study was undertaken to examine the physical and physiological interaction of protein phosphatase 2B, calcineurin, with the ryanodine receptor (RyR) in rat cardiac tissue and neonatal cardiomyocytes. The presence of calcineurin, the RyR and FK506-binding protein (FKBP)12.6 in rat cardiac sarcoplasmic reticulum (SR) was identified by Western blot analysis. The possible interactions between calcineurin, the RyR and FKBP12.6 were further studied by co-immunoprecipitation using CHAPS-solubilized cardiac-membrane fractions (CSMFs) or SR preparations. Physical interactions between the RyR and calcineurin were found in the CSMF in the presence of added 100 microM Ca(2+); however, the interactions were interrupted in the presence of 20 mM EGTA, 1 microM rapamycin or 1 microM FK506, suggesting that the interaction is Ca(2+)-dependent, and is mediated by FKBP12.6. The Ca(2+)-dependent interaction between FKBP12.6 and the RyR was also found by co-immunoprecipitation. Effects of calcineurin inhibitors were tested on neonatal-rat-heart cardiomyocytes. Treatment of neonatal cardiomyocytes with 20 microM deltamethrin, 10 microM cyclosporin A (CsA), or 10 mciroM FK506 led to Ca(2+) oscillations in originally quiescent cardiomyocytes. Preincubation of cardiomyocytes with 20 microM rapamycin which dissociates FKBP12.6 from the RyR, evoked Ca(2+) oscillations, probably due to the leakiness of the RyR. However, Ca(2+) oscillations by rapamycin were not further affected by 10 microM CsA or 10 mciroM deltamethrin, suggesting that only RyR-associated calcineurin could regulate the channel activities. In spontaneously Ca(2+)-oscillating cardiomyocytes, CsA or FK506 treatments increased the frequency of oscillations. In 10 microM ryanodine-treated cardiomyocytes, CsA failed to induce Ca(2+) oscillations. These data show evidence that calcineurin associated with the RyR could modulate Ca(2+) release in rat heart.

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Section: Discussionsupporting

confidence: 85%

Calcineurin regulates ryanodine receptor/Ca2+-release channels in rat heart

et al. 2000

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“…Here we showed strong HSP25 and aB-crystallin positivity in all aortic tunicas after CsA treatment, so its expression may be related to the reorganization of intermediate filaments in these layers. In fact, previous data showed a direct toxic effect of CsA on the structure and spatial arrangements of the cytoskeleton and on the expression of vimentin and desmin in cells of rat thymus in vivo [35] and in chick embryo cardiomyocytes [36]. For this reason, we suggest that HSP25 and aB-crystallin expression is induced as protective proteins to modulate or reduce the toxic effects on cytoskeleton network.…”

Section: Discussionmentioning

confidence: 65%

Cyclosporine A induces vascular fibrosis and heat shock protein expression in rat

Rezzani

Rodella

Buffoli

et al. 2005

International Immunopharmacology

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Knockdown endogenous CypA with siRNA in U2OS cells results in disruption of F-actin structure and alters tumor phenotype

Calhoun¹,

Lu²,

Song³

et al. 2008

Mol Cell Biochem

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Cyclophilin A (CypA) was originally identified as a cytosolic protein possessing peptidyl-prolyl isomerase activity. CypA has been shown to play a pivotal role in the immune response, but little is known about other molecular mechanisms of CypA-mediated biologic events. In our present study, we demonstrate that knockdown CypA expression using RNAi in U2OS cells resulted in disruption of the F-actin structure, as well as decreased anchorage-independent growth, proliferation, and migration. Wild-type U2OS cells treated with cyclosporine A (CsA), a peptidyl-prolyl isomerase inhibitor, displayed the same phenotype as knockdown CypA cells, suggesting that the isomerase activity of CypA is required to maintain a normal phenotype. In vitro and in vivo binding assays revealed that CypA binds to N-WASP, which functions in the nucleation of actin via the Arp2/3 complex. Pulse-chase labeling study indicated an enhanced degradation of N-WASP in cell lacking CypA, suggesting that CypA is required for stabilizing N-WASP to form a N-WASP/Arp2/3 complex for the nucleation/initiation of F-actin polymerization.

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Effects of cyclosporin A on contractile activity and cytoskeleton in chick embryo cardiomyocytes

Cited by 3 publications

References 0 publications

Calcineurin regulates ryanodine receptor/Ca2+-release channels in rat heart

Calcineurin regulates ryanodine receptor/Ca2+-release channels in rat heart

Cyclosporine A induces vascular fibrosis and heat shock protein expression in rat

Knockdown endogenous CypA with siRNA in U2OS cells results in disruption of F-actin structure and alters tumor phenotype

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