title: Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg2+, NF-κB, and de novo ceramide.
abstract: The present study tested the hypotheses that 1) short-term dietary deficiency (MgD) of magnesium (21 days) would result in the upregulation of ceramide synthase (CS) in left ventricular (LV), right ventricular, atrial, and aortic smooth muscle, as well as induce a synthesis/release of select cytokines and chemokines into the LV and aortic smooth muscle and serum; 2) exposure of primary cultured vascular smooth muscle cells (VSMCs) to low extracellular Mg concentration would lead to the synthesis/release of select cytokines/chemokines, activation of N-SMase, and the de novo synthesis of ceramide; and 3) inhibition of CS by fumonisin B1 (FB1) or inhibition of neutral sphingomyelinase (N-SMase) by scyphostatin (SCY) in VSMCs exposed to low Mg would result in reductions in the levels of the cytokines/chemokines and lowered levels of ceramide concomitant with inhibition of NF-κB activation. The data indicated that short-term MgD (10% normal dietary intake) resulted in the upregulation of CS in ventricular, atrial, and aortic smooth muscles coupled to the synthesis/release of 12 different cytokines/chemokines, as well as activation of NF-κB in the LV and aortic smooth muscle and sera; even very low levels of water-borne Mg (e.g., 15 mg·l(-1)·day(-1)) either prevented or ameliorated the upregulation and synthesis of the cytokines/chemokines. Our experiments also showed that VSMCs exposed to low extracellular Mg resulted in the synthesis of 5 different cytokines and chemokines concomitant with synthesis/release of ceramide. However, inhibition of the synthesis and release of ceramide by either FB1 or SCY attenuated, markedly , the generation of ceramide, release of the cytokines/chemokines, and activation of NF-κB (as measured by activated p65 and cRel).
authors: Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, 11203, USA. baltura@downstate.edu
authors: Burton M
authors: BM
authors: Altura
authors: Nilank C
authors: NC
authors: Shah
authors: Gatha
authors: G
authors: Shah
authors: Aimin
authors: A
authors: Zhang
authors: Wenyan
authors: W
authors: Li
authors: Tao
authors: T
authors: Zheng
authors: Jose Luis
authors: JL
authors: Perez-Albela
authors: Bella T
authors: BT
authors: Altura
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004032:Diet; D004195:Disease Models, Animal; D004326:Drinking; D004435:Eating; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D037341:Fumonisins / Q000494:pharmacology; D006325:Heart Atria / Q000201:enzymology; D006352:Heart Ventricles / Q000201:enzymology; D008274:Magnesium / Q000008:administration & dosage / Q000378:metabolism*; D008275:Magnesium Deficiency / Q000201:enzymology* / Q000517:prevention & control; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology*; D016328:NF-kappa B / Q000378:metabolism*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology; D051381:Rats; D012044:Regression Analysis; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000577:Amides; D002518:Ceramides; D016207:Cytokines; D004791:Enzyme Inhibitors; D037341:Fumonisins; D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel; D011753:Pyrones; C498145:Rela protein, rat; D051996:Transcription Factor RelA; C121123:scyphostatin; C056933:fumonisin B1; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; D013108:Sphingomyelin Phosphodiesterase; D008274:Magnesium