کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1994738 1541289 2014 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Oxidative stress modulates nucleobase transport in microvascular endothelial cells
ترجمه فارسی عنوان
استرس اکسیداتیو، انتقال سلول های بنیادی مغز استخوان را در سلول های اندوتلیوم میکروارگالی مود
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
چکیده انگلیسی


• HMEC-1 are similar to CMVEC in nucleoside/nucleobase transport characteristics.
• A model of simulated ischemia/reperfusion (sI/R) produces intracellular superoxide.
• Intracellular superoxide generation down-regulates ENBT1 hypoxanthine transport.
• Decreased hypoxanthine efflux by ENBT1 may aggravate vascular dysfunction in I/R.

Purine nucleosides and nucleobases play key roles in the physiological response to vascular ischemia/reperfusion events. The intra- and extracellular concentrations of these compounds are controlled, in part, by equilibrative nucleoside transporter subtype 1 (ENT1; SLC29A1) and by equilibrative nucleobase transporter subtype 1 (ENBT1). These transporters are expressed at the membranes of numerous cell types including microvascular endothelial cells. We studied the impact of reactive oxygen species on the function of ENT1 and ENBT1 in primary (CMVEC) and immortalized (HMEC-1) human microvascular endothelial cells. Both cell types displayed similar transporter expression profiles, with the majority (> 90%) of 2-chloro[3H]adenosine (nucleoside) uptake mediated by ENT1 and [3H]hypoxanthine (nucleobase) uptake mediated by ENBT1. An in vitro mineral oil-overlay model of ischemia/reperfusion had no effect on ENT1 function, but significantly reduced ENBT1 Vmax in both cell types. This decrease in transport function was mimicked by the intracellular superoxide generator menadione and could be reversed by the superoxide dismutase mimetic MnTMPyP. In contrast, neither the extracellular peroxide donor TBHP nor the extracellular peroxynitrite donor 3-morpholinosydnonimine (SIN-1) affected ENBT1-mediated [3H]hypoxanthine uptake. SIN-1 did, however, enhance ENT1-mediated 2-chloro[3H]adenosine uptake. Our data establish HMEC-1 as an appropriate model for study of purine transport in CMVEC. Additionally, these data suggest that the generation of intracellular superoxide in ischemia/reperfusion leads to the down-regulation of ENBT1 function. Modification of purine transport by oxidant stress may contribute to ischemia/reperfusion induced vascular damage and should be considered in the development of therapeutic strategies.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Microvascular Research - Volume 95, September 2014, Pages 68–75
نویسندگان
, , , ,