کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6264103 1613956 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research ReportPPARδ agonist GW501516 prevents uncoupling of endothelial nitric oxide synthase in cerebral microvessels of hph-1 mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Research ReportPPARδ agonist GW501516 prevents uncoupling of endothelial nitric oxide synthase in cerebral microvessels of hph-1 mice
چکیده انگلیسی

Peroxisome proliferator-activated receptor delta (PPARδ) is ubiquitously expressed in the vasculature, including cerebral circulation. The role of PPARδ in metabolism of tetrahydrobiopterin (BH4) has not been studied in the cerebral microvasculature. In the present study, the effects of PPARδ agonist GW501516 on uncoupling of endothelial nitric oxide synthase (eNOS) were determined in cerebral microvessels of BH4-deficient hph-1 mice. Wild-type (B6CBA) and hph-1 mice were orally gavaged with a selective PPARδ activator, GW501516 (2 mg/kg/day) for 14 days, and thereafter, cerebral microvessels were isolated and studied. Treatment of hph-1 mice with GW501516 significantly reduced oxidation of BH4 and increased the ratio of BH4 to 7,8-BH2 (P<0.05, n=6-9). Attenuation of L-NAME-inhibitable superoxide anion levels by GW501516 demonstrated that activation of PPARδ might prevent uncoupling of endothelial nitric oxide synthase (eNOS, P<0.05, n=6-9). Western blotting studies demonstrated that GW501516 selectively increased the endothelial expressions of CuZn superoxide dismutase (P<0.05, n=6-9) and catalase (P<0.05, n=6-8). PPARδ activation increased the total nitrite and nitrate (NO2+NO3) content in cerebral microvessels (P<0.05, n=6). Obtained results suggest that in vivo activation of PPARδ prevents eNOS uncoupling, restores bioavailability of NO and may help preserve endothelial function in the BH4-deficient cerebral circulation.

► We studied the effects of GW501516 in cerebral microvessels of hph-1 mice. ► Selective PPARδ agonist GW501516 significantly increased bioavailability of BH4. ► GW501516 reversed eNOS uncoupling and increased nitrite/nitrate content. ► GW501516 may preserve endothelial function in BH4-deficient cerebral circulation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1483, 5 November 2012, Pages 89-95
نویسندگان
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