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

被引:36
作者
Altura, BM
Gebrewold, A
Zhang, AM
Altura, BT
机构
[1] SUNY Downstate Med Ctr, Dept Physiol, Brooklyn, NY 11203 USA
[2] SUNY Downstate Med Ctr, Dept Pharmacol, Brooklyn, NY 11203 USA
[3] SUNY Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA
[4] SUNY Downstate Med Ctr, Ctr Cardiovasc & Muscle Res, Brooklyn, NY 11203 USA
关键词
Mg2+ deficits; vascular smooth muscle; nuclear transcription factor kappa B; I kappa B; reactive oxygen species; lipid peroxidation; stroke; traumatic brain injury;
D O I
10.1016/S0304-3940(03)00134-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The present study was designed to test the hypothesis that administration of low extracellular levels of magnesium ions ([Mg2+](o)) to primary cultured cerebral vascular smooth muscle cells will cause lipid peroxidation, degradation Of IbetaB-alpha, and activation of nuclear transcription factor kappa B (NF-kappaB) in cultured cerebral vascular smooth muscle cells. Low [Mg2+](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 [Mg2+](o), rising to levels 3-12 X normal after 18-24 h; the lower the [Mg2+](o), the higher the MDA level. Using electrophoretic mobility shift assays and specific antibodies, low [Mg2+](o) caused two DNA-binding proteins (p50, p65) to rise in nuclear extracts in a concentration-dependent manner. High [Mg2+](o) (i.e. 4.8 mM) downregulated p50 and p65. Using a rabbit antibody, IkappaB phosphorylation (and degradation) was stimulated by low [Mg2+](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 [Mg2+](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 [Mg2+](o)-induced lipid peroxidation and activation of NF-kappaB play important roles in TBI and diverse types of strokes. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:189 / 192
页数:4
相关论文
共 23 条
[1]   Magnesium deficiency exacerbates brain injury and stroke mortality induced by alcohol:: A 31P-NMR in vivo study [J].
Altura, BM ;
Gebrewold, A ;
Zhang, AM ;
Altura, BT ;
Gupta, RK .
ALCOHOL, 1998, 15 (03) :181-183
[2]   Short-term reduction in dietary intake of magnesium causes deficits in brain intracellular free Mg2+ and [H+](i) but not high-energy phosphates as observed by in vivo P-31-NMR [J].
Altura, BM ;
Gebrewold, A ;
Zhang, AM ;
Altura, BT ;
Gupta, RK .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1997, 1358 (01) :1-5
[3]   ROLE OF MAGNESIUM AND CALCIUM IN ALCOHOL-INDUCED HYPERTENSION AND STROKES AS PROBED BY IN-VIVO TELEVISION MICROSCOPY, DIGITAL IMAGE MICROSCOPY, OPTICAL SPECTROSCOPY, P-31-NMR, SPECTROSCOPY AND A UNIQUE MAGNESIUM ION-SELECTIVE ELECTRODE [J].
ALTURA, BM ;
ALTURA, BT .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 1994, 18 (05) :1057-1068
[4]   ROLE OF BRAIN [MG2+](I) IN ALCOHOL-INDUCED HEMORRHAGIC STROKE IN A RAT MODEL - A P-31-NMR IN-VIVO STUDY [J].
ALTURA, BM ;
GEBREWOLD, A ;
ALTURA, BT ;
GUPTA, RK .
ALCOHOL, 1995, 12 (02) :131-136
[5]  
ALTURA BM, 1997, MAGNESIUM CURRENT ST, P385
[6]  
ALTURA BM, 1995, SCI AM SCI MED, V2, P28
[7]   Low levels of serum ionized magnesium are found in patients early after stroke which result in rapid elevation in cytosolic free calcium and spasm in cerebral vascular muscle cells [J].
Altura, BT ;
Memon, ZI ;
Zhang, AM ;
Cheng, TPO ;
Silverman, R ;
Cracco, RQ ;
Altura, BM .
NEUROSCIENCE LETTERS, 1997, 230 (01) :37-40
[8]  
[Anonymous], MAGNESIUM
[9]  
BAICHWAL VR, 1997, PHARM NEWS, V4, P17
[10]   Alterations in ionized and total blood magnesium after experimental traumatic brain injury: Relationship to neurobehavioral outcome and neuroprotective efficacy of magnesium chloride [J].
Bareyre, FM ;
Saatman, KE ;
Helfaer, MA ;
Sinson, G ;
Weisser, JD ;
Brown, AL ;
McIntosh, TK .
JOURNAL OF NEUROCHEMISTRY, 1999, 73 (01) :271-280