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.

Abstract:

: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.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Altura BM,Gebrewold A,Zhang A,Altura BT

doi

10.1016/s0304-3940(03)00134-4

keywords:

subject

Has Abstract

pub_date

2003-05-08 00:00:00

pages

189-92

issue

3

eissn

0304-3940

issn

1872-7972

pii

S0304394003001344

journal_volume

341

pub_type

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