کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2553249 1560725 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dexamethasone-induced cardioprotection: A role for the phosphatase MKP-1?
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Dexamethasone-induced cardioprotection: A role for the phosphatase MKP-1?
چکیده انگلیسی

AimsPrevious studies suggested that p38 MAPK activation during sustained myocardial ischaemia and reperfusion was harmful. We hypothesize that attenuation of p38MAPK activity via dephosphorylation by the dual-specificity phosphatase MKP-1 should be protective against ischaemia/reperfusion injury. Since the glucocorticoid, dexamethasone, induces the expression of MKP-1, the aim of this study was to determine whether upregulation of this phosphatase by dexamethasone protects the heart against ischaemia/reperfusion injury.Main methodsMale Wistar rats were treated with dexamethasone (3 mg/kg/day ip) for 10 days, before removal of the hearts for Western blot (ip Dex − P) or perfusion in the working mode (ip Dex + P). Hearts were subjected to 20 min global or 35 min regional ischaemia (36.5 °C) and 30 or 120 min reperfusion. In a separate series, dexamethasone (1 µM) was added to the perfusate for 10 min (Pre + Dex) before or after (Rep + Dex) ischaemia.Key findingsDexamethasone, administered intraperitoneally or added directly to the perfusate, significantly improved post-ischaemic functional recovery and reduced infarct size compared to untreated controls (p < 0.05). These were associated with enhanced up-regulation of MKP-1 protein expression (arbitrary units (mean ± SD): Untreated: 1; ip Dex − P: 2.59 ± 0.22; ip Dex + P: 1.51 ± 0.22; Pre + Dex: 4.11 ± 0.73, Rep + 15′Dex: 1.51 ± 0.14; untreated vs. all groups, p < 0.05) and attenuation of p38 MAPK activation (p < 0.05) in all dexamethasone-treated groups, except for Rep + 10′Dex. ERK and PKB/Akt activation were unchanged.SignificanceDexamethasone-induced cardioprotection was associated with upregulation of the phosphatase MKP-1 and inactivation of pro-apoptotic p38 MAPK.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 84, Issues 23–24, 5 June 2009, Pages 838–846
نویسندگان
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