Expression of the nuclear factor-kappaB and proto-oncogenes c-fos and c-jun are induced by low extracellular Mg2+ in aortic and cerebral vascular smooth muscle cells: possible links to hypertension, atherogenesis, and stroke.
Proto-oncogene (c-fos, c-jun) and nuclear factor-kappa B (NF-kappaB) expression, as well as DNA synthesis, in aortic and cerebral vascular smooth muscle cells (VSMCs) were upregulated by a decrease in extracellular magnesium ions ([Mg2+]o). Upregulation of these transcriptional factors was inversely proportional to the [Mg2+]o and occurred over the pathophysiologic range of serum Mg2+ found in patients presenting with hypertension, ischemic heart disease, and stroke. Removal of extracellular Ca2+ ([Ca2+]o), use of nifedipine or protein kinase C (PKC) inhibitors prevented the upregulation of the proto-oncogenes and DNA synthesis in VSMCs. These data show that [Mg2+]o may be an important, heretofore, overlooked natural modulator of proto-oncogene and NF-kappaB expression in VSMCs and that Ca2+ and PKC may play critical roles in induction of c-fos and c-jun in VSMCs induced by a decrease in [Mg2+]o. These results point to a role for low serum Mg2+ in potential development of hypertension, atherogenesis, vascular disease, and stroke.
Altura
Burton M
BM
Department of Physiology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. baltura@downstate.edu
Kostellow
Adele B
AB
Zhang
Aimin
A
Li
Wenyan
W
Morrill
Gene A
GA
Gupta
Raj K
RK
Altura
Bella T
BT
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002318:Cardiovascular Diseases; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D016762:Genes, fos / Q000187:drug effects* / Q000502:physiology*; D016758:Genes, jun / Q000187:drug effects* / Q000502:physiology*; D006973:Hypertension / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis* / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology* / Q000187:drug effects*; D013997:Time Factors
D015415:Biomarkers; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D012333:RNA, Messenger; D004247:DNA; D011493:Protein Kinase C; D008274:Magnesium; D009543:Nifedipine; D002118:Calcium