Low extracellular magnesium ions induce lipid peroxidation and activation of nuclear factor-kappa B in canine cerebral vascular smooth muscle: possible relation to traumatic brain injury and strokes.
The present study was designed to test the hypothesis that administration of low extracellular levels of magnesium ions ([Mg(2+)](o)) to primary cultured cerebral vascular smooth muscle cells will cause lipid peroxidation, degradation of IkappaB-alpha, and activation of nuclear transcription factor kappa B (NF-kappaB) in cultured cerebral vascular smooth muscle cells. Low [Mg(2+)](o) (0, 0.15, 0.3 and 0.48 mM) resulted in concentration-dependent rises in malondialdehyde (MDA) in as little as 3 h after exposure to low [Mg(2+)](o), rising to levels 3-12xnormal after 18-24 h; the lower the [Mg(2+)](o), the higher the MDA level. Using electrophoretic mobility shift assays and specific antibodies, low [Mg(2+)](o) caused two DNA-binding proteins (p50, p65) to rise in nuclear extracts in a concentration-dependent manner. High [Mg(2+)](o) (i.e. 4.8 mM) downregulated p50 and p65. Using a rabbit antibody, IkappaB phosphorylation (and degradation) was stimulated by low [Mg(2+)](o) (in a concentration-dependent manner) and inhibited by a low concentration of the NF-kappaB inhibitor, pyrrolidine dithiocarbamate. These new biochemical and molecular data indicate that low [Mg(2+)](o), in concentrations found in the blood of patients, after traumatic brain injury (TBI) and diverse types of strokes, can elicit rapid lipid peroxidation and activation of NF-kappaB in cerebral vascular smooth muscle cells. The present results, when viewed in light of other recently published data, suggest that low [Mg(2+)](o)-induced lipid peroxidation and activation of NF-kappaB play important roles in TBI and diverse types of strokes.
Altura
Burton M
BM
Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, Brooklyn 11203, USA. baltura@downstate.edu
Gebrewold
Asefa
A
Zhang
Aimin
A
Altura
Bella T
BT
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism*
D016328:NF-kappa B; D008274:Magnesium