کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1930049 1050488 2012 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and use of cell-permeant cyclic ADP-ribose
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Synthesis and use of cell-permeant cyclic ADP-ribose
چکیده انگلیسی

Cyclic ADP-ribose (cADPR) is a second messenger that acts on ryanodine receptors to mobilize Ca2+. cADPR has a net negative charge at physiological pH making it not passively membrane permeant thereby requiring it to be injected, electroporated or loaded via liposomes. Such membrane impermeance of other charged intracellular messengers (including cyclic AMP, inositol 1,4,5-trisphosphate and nicotinic acid adenine dinucleotide phosphate) and fluorescent dyes (including fura-2 and fluorescein) has been overcome by synthesizing masked analogs (prodrugs), which are passively permeant and hydrolyzed to the parent compound inside cells. We now report the synthesis and biological activity of acetoxymethyl (AM) and butoxymethyl (BM) analogs of cADPR. Extracellular addition of cADPR-AM or cADPR-BM to neuronal cells in primary culture or PC12 neuroblastoma cells induced increases in cytosolic Ca2+. Pre-incubation of PC12 cells with thapsigargin, ryanodine or caffeine eliminated the response to cADPR-AM, whereas the response still occurred in the absence of extracellular Ca2+. Combined, these data demonstrate that masked cADPR analogs are cell-permeant and biologically active. We hope these cell-permeant tools will facilitate cADPR research and reveal its diverse physiological functions.


► We synthesized analogs of cADPR with acetoxymethyl and butoxymethyl groups.
► These analogs of cADPR are cell-permeant and biologically active in neurons.
► Pharmacology of the cADPR analogs indicates action at the endoplasmic reticulum.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 418, Issue 2, 10 February 2012, Pages 353–358
نویسندگان
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