title: Extracellular magnesium regulates effects of vitamin B6, B12 and folate on homocysteinemia-induced depletion of intracellular free magnesium ions in canine cerebral vascular smooth muscle cells: possible relationship to [Ca2+]i, atherogenesis and stroke.
abstract: Homocysteine (HC) at concentrations of from 0.05 to 1.0 mM caused dose-dependent loss of [Mg2+]i in cultured cerebral vascular smooth muscle cells (VSMC), whereas cysteine and methionine (its metabolic products) failed to interfere with changes in [Mg2+]i. HC, methionine and cysteine did not produce any changes in [Ca2+]i. Lowering [Mg2+]o to 0.3 mM resulted in elevation of [Ca2+]i and loss of [Mg2+]i. Depletion of [Mg2+]i, induced by HC, was potentiated by low Mg2+. Preincubation of these cells with vitamin B6, vitamin B12, folic acid, alone, did not alter [Ca2+]i or [Mg2+]i. Likewise, concomitant addition of vitamin B6, vitamin B12, or folic acid, together with HC (1 mM) did not change the reduction in [Mg2+]i induced by HC. However, concomitant addition of HC and the three vitamins inhibited completely the loss of [Mg2+]i. Exposure of these cells to each vitamin, alone, or combination of the three vitamins failed to interfere with reduction in [Mg2+]i induced by low [Mg2+]i, but it did suppress the rise in [Ca2+]i. Interestingly, in the presence of low [Mg2+]o, the vitamin combination did not retard depletion of [Mg2+]i. The present findings are compatible with the hypothesis that an increased serum HC concentration causes abnormal metabolism of Mg2+ in cerebral VSMC, thus priming these cells for HC-induced atherogenesis, cerebral vasospasm and stroke. Our results suggest the need for the three B-vitamins, together with normal physiological levels of Mg2+, in order to prevent [Mg2+]i depletion and occlusive cerebral vascular diseases induced by homocysteinemia.
authors.affiliation: Department of Physiology, State University of New York, Health Science Center at Brooklyn, 11203, USA.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Zheng
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: B T
authors.initials: BT
authors.lastname: Altura
authors.forename: B M
authors.initials: BM
authors.lastname: Altura
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D001488:Basilar Artery / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000166:cytology; D004285:Dogs; D005492:Folic Acid / Q000494:pharmacology; D006710:Homocysteine / Q000097:blood / Q000494:pharmacology; D020138:Hyperhomocysteinemia / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011736:Pyridoxine / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D020521:Stroke / Q000378:metabolism; D014805:Vitamin B 12 / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D014815:Vitamins; D006710:Homocysteine; D005492:Folic Acid; D008274:Magnesium; D011736:Pyridoxine; D014805:Vitamin B 12; D002118:Calcium