Magnesium deficiency upregulates serine palmitoyl transferase (SPT 1 and SPT 2) in cardiovascular tissues: relationship to serum ionized Mg and cytochrome c.
The present work tested the hypothesis that a short-term dietary deficiency of magnesium (Mg) (21 days) in rats would result in the upregulation of the two major subunits of serine palmitoyl-CoA-transferase, serine palmitoyl transferase (SPT 1) and SPT 2 (the rate-limiting enzymes responsible for the de novo biosynthesis of ceramides) in left ventricular, right ventricular, and atrial heart muscle and abdominal aortic smooth muscle, as well as induce a reduction in serum sphingomyelin concomitant with the release of mitochondrial cytochrome c (Cyto c) in these tissues. Our data indicate that short-term Mg deficiency (MgD) resulted in an upregulation of SPT 1 and SPT 2, concomitant with a very significant release of Cyto c in left ventricular, right ventricular, atrial, and abdominal aortic smooth muscle. Short-term MgD also produced a lowering of serum sphingomyelin and ionized Mg. The greater the reduction in serum ionized Mg, the greater the upregulation of SPT 1 and 2 and the more the increase in free Cyto c. The data suggest that MgD, most likely, causes a biosynthesis of ceramides via two pathways in cardiovascular tissues, viz., via the activation of serine palmitoyl-CoA-transferase and sphingomyelinase, which lead to apoptotic events via intrinsic (present study) and extrinsic pathways (previous studies). Low levels of drinking water Mg were cardio- and vasculoprotective.
Altura
Burton M
BM
Department of Physiology and Pharmacology, SUNY Downstate Medical Ctr., 450 Clarkson Ave., Brooklyn, NY, 11203-2098, USA. baltura@downstate.edu
Shah
Nilank C
NC
Li
Zhiqiang
Z
Jiang
Xian-Cheng
XC
Perez-Albela
Jose Luis
JL
Altura
Bella T
BT
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002518:Ceramides / Q000097:blood; D045304:Cytochromes c / Q000378:metabolism*; D005260:Female; D008274:Magnesium / Q000097:blood*; D008275:Magnesium Deficiency / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D051102:Serine C-Palmitoyltransferase / Q000378:metabolism*; D013109:Sphingomyelins / Q000097:blood; D015854:Up-Regulation
D002518:Ceramides; D013109:Sphingomyelins; D045304:Cytochromes c; D051102:Serine C-Palmitoyltransferase; D008274:Magnesium