Reperfusion Therapy with Rapamycin Attenuates Myocardial Infarction through Activation of AKT and ERK
Joint Authors
Kukreja, Rakesh C.
Das, Anindita
Filippone, Scott M.
Samidurai, Arun
Roh, Sean K.
Cain, Chad K.
He, Jun
Salloum, Fadi N.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-03-08
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
Prompt coronary reperfusion is the gold standard for minimizing injury following acute myocardial infarction.
Rapamycin, mammalian target of Rapamycin (mTOR) inhibitor, exerts preconditioning-like cardioprotective effects against ischemia/reperfusion (I/R) injury.
We hypothesized that Rapamycin, given at the onset of reperfusion, reduces myocardial infarct size through modulation of mTOR complexes.
Adult C57 male mice were subjected to 30 min of myocardial ischemia followed by reperfusion for 1 hour/24 hours.
Rapamycin (0.25 mg/kg) or DMSO (7.5%) was injected intracardially at the onset of reperfusion.
Post-I/R survival (87%) and cardiac function (fractional shortening, FS: 28.63±3.01%) were improved in Rapamycin-treated mice compared to DMSO (survival: 63%, FS: 17.4±2.6%).
Rapamycin caused significant reduction in myocardial infarct size (IS: 26.2±2.2%) and apoptosis (2.87±0.64%) as compared to DMSO-treated mice (IS: 47.0±2.3%; apoptosis: 7.39±0.81%).
Rapamycin induced phosphorylation of AKT S473 (target of mTORC2) but abolished ribosomal protein S6 phosphorylation (target of mTORC1) after I/R.
Rapamycin induced phosphorylation of ERK1/2 but inhibited p38 phosphorylation.
Infarct-limiting effect of Rapamycin was abolished with ERK inhibitor, PD98059.
Rapamycin also attenuated Bax and increased Bcl-2/Bax ratio.
These results suggest that reperfusion therapy with Rapamycin protects the heart against I/R injury by selective activation of mTORC2 and ERK with concurrent inhibition of mTORC1 and p38.
American Psychological Association (APA)
Filippone, Scott M.& Samidurai, Arun& Roh, Sean K.& Cain, Chad K.& He, Jun& Salloum, Fadi N.…[et al.]. 2017. Reperfusion Therapy with Rapamycin Attenuates Myocardial Infarction through Activation of AKT and ERK. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-16.
https://search.emarefa.net/detail/BIM-1194766
Modern Language Association (MLA)
Filippone, Scott M.…[et al.]. Reperfusion Therapy with Rapamycin Attenuates Myocardial Infarction through Activation of AKT and ERK. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-16.
https://search.emarefa.net/detail/BIM-1194766
American Medical Association (AMA)
Filippone, Scott M.& Samidurai, Arun& Roh, Sean K.& Cain, Chad K.& He, Jun& Salloum, Fadi N.…[et al.]. Reperfusion Therapy with Rapamycin Attenuates Myocardial Infarction through Activation of AKT and ERK. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-16.
https://search.emarefa.net/detail/BIM-1194766
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1194766