Phosphorylation of AktSer473/Ask1Ser83 in Trolox-induced suppression of doxorubicin-induced changes in rat cardiomyocytes

Sharma, Anita; Bagchi, Ashim K.; Al‐Shudiefat, Abd Al‐Rahman; Akolkar, Gauri; Jassal, Davinder S.; Singal, Pawan K.

doi:10.4172/2368-0512.1000003

Cited by 1 publication

(1 citation statement)

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“…Under nonstimulated conditions, Thr 495 is phosphorylated, whereas stimulation by estrogen, VEGF, or bradykinin activates eNOS through phosphorylation at Ser 1177 through Akt/AMPK (15). Downregulation of Akt and AMPK has been reported in Dox-treated cardiomyocytes (27,43). These Dox-mediated changes in eNOS phosphorylation were reversed by Vit C. Vit C pretreatment increased the phosphorylation of eNOS at Ser 1177 while it reduced Thr 495 phosphorylation in Dox-treated cardiomyocytes.…”

Section: Vit C Enhances Enos Stabilization In Its Dimeric Formmentioning

confidence: 94%

Doxorubicin-induced nitrosative stress is mitigated by vitamin C via the modulation of nitric oxide synthases

Akolkar

Bagchi

Ayyappan

et al. 2017

American Journal of Physiology-Cell Physiology

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An increase in oxidative stress is suggested to be the main cause in Doxorubicin (Dox)-induced cardiotoxicity. However, there is now evidence that activation of inducible nitric oxide synthase (iNOS) and nitrosative stress are also involved. The role of vitamin C (Vit C) in the regulation of nitric oxide synthase (NOS) and reduction of nitrosative stress in Dox-induced cardiotoxicity is unknown. The present study investigated the effects of Vit C in the mitigation of Dox-induced changes in the levels of nitric oxide (NO), NOS activity, protein expression of NOS isoforms, and nitrosative stress as well as cytokines TNF-α and IL-10 in isolated cardiomyocytes. Cardiomyocytes isolated from adult Sprague-Dawley rats were segregated into four groups: ) control,) Vit C (25 µM), ) Dox (10 µM), and) Vit C + Dox. Dox caused a significant increase in the generation of superoxide radical (O), peroxynitrite, and NO, and these effects of Dox were blunted by Vit C. Dox increased the expression of iNOS and altered protein expression as well as activation of endothelial NOS (eNOS). These changes were prevented by Vit C. Dox induced an increase in the ratio of monomeric/dimeric eNOS, promoting the production of O, which was prevented by Vit C by increasing the stability of the dimeric form of eNOS. Vit C protected against the Dox-induced increase in TNFα as well as a reduction in IL-10. These results suggest that Vit C provides cardioprotection by reducing oxidative/nitrosative stress and inflammation via a modulation of Dox-induced increase in the NO levels and NOS activity.

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Section: Vit C Enhances Enos Stabilization In Its Dimeric Formmentioning

confidence: 94%