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• W2914982543 abstract "The role of 2,4-diamino-6-hydroxypyrimidine (DAHP), on cellular-senescence remains unclear as differential effects of DAHP have been reported in cardiovascular and cerebrovascular systems. We investigated the effect of pharmacologically-induced guanosine-triphosphate-cyclohydrolase1 (GTPCH1)-inhibition, through DAHP, on cellular-senescence in experimentally-induced diabetic and non-diabetic Wistar rats. Cellular-senescence was evaluated through senescence-associated events, namely, cell-cycle-arrest of peripheral blood mononuclear cells (PBMNCs); myocardial DNA fragmentation, total antioxidant capacity (TAC), telomerase-activity, nicotinamide adenine dinucleotide (NAD+)-content and tyrosine14-phosphorylation of caveolin1 (pY14) in similarly-aged, pubertal Wistar rats with streptozotocin (STZ) and/or DAHP. Oxidative stress (OS) indices such as myocardial biopterin concentrations (tetrahydrobiopterin-BH4 and dihydrobiopterin-BH2) and plasma total nitrite and nitrate (NOx) were determined. DAHP, per se, exhibited distinct senescence; in addition, in STZ+DAHP (the cardiomyopathy model), there was a marked accumulation of cells in G0G1 phase, as evidenced through flow-cytometry analysis, as-well-as fragmented DNA, than the respective controls suggesting the DAHP-mediated onset of senescence in circulating cells and the myocardium, with or without STZ. Concentrations of BH4 and BH2, and NOx were impaired in STZ and/or DAHP, indicating elevated OS in the treatment groups. In the independent treatment groups or the combination treatment, typical senescence indicators including myocardial telomerase-activity, NAD+-content and TAC were significantly reduced, while there was a marked elevation in the concentrations of pY14 as compared to the respective controls, reinforcing the occurrence of senescence in PBMNCs and the myocardium. We postulate that DAHP promotes early onset of cellular-senescence, potentially through OS-mediated cellular events in diabetic or non-diabetic models." @default.
• W2914982543 created "2019-02-21" @default.
• W2914982543 creator A5011718142 @default.
• W2914982543 creator A5027963169 @default.
• W2914982543 creator A5029430052 @default.
• W2914982543 creator A5036823611 @default.
• W2914982543 creator A5044024787 @default.
• W2914982543 creator A5071756086 @default.
• W2914982543 creator A5089343498 @default.
• W2914982543 date "2019-04-01" @default.
• W2914982543 modified "2023-10-16" @default.
• W2914982543 title "Pharmacological inhibition of guanosine triphosphate cyclohydrolase1 elevates tyrosine phosphorylation of caveolin1 and cellular senescence" @default.
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