Regulation of myosin isozyme expression by vitamin D3 deficiency and 1,25-dihydroxyvitamin D3 in the rat heart.
In this report, we demonstrate a significant inverse correlation between contractility and serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] levels and no correlation between contractility and serum levels of calcium, phosphate, or PTH. We also examined myosin isozyme distribution in vitamin D3-deficient rats, because myosin isozyme distribution can alter contractility. There was a significant increase in the levels of the V1 myosin isozyme in animals raised on a vitamin D3-deficient diet that maintained normal serum calcium and phosphate levels. There was no difference in the relative myosin isozyme distribution in animals raised on a hypocalcemia-yielding vitamin D3-deficient diet vs. animals raised on a control diet. As increased contractility has been observed in both groups of vitamin D3-deficient animals, a shift in myosin isozyme distribution cannot solely explain the increase in contractility previously observed in the vitamin D3-deficient rat heart. To determine whether 1,25-(OH)2D3 directly regulates myosin isozyme levels, we analyzed myosin isozyme distribution in primary cultures of ventricular myocytes. We found that 1,25-(OH)2D3 reduces total myosin levels, but does not alter myosin isozyme distribution. Thus, we show that the influence of vitamin D3 status on myosin isozyme expression in the intact rat involves a complex regulatory system of direct and indirect effects.
O'Connell
T D
TD
Department of Pharmacology, University of Michigan, Ann Arbor 48109-0626.
Weishaar
R E
RE
Simpson
R U
RU
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000097:blood / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000302:isolation & purification; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000096:biosynthesis* / Q000302:isolation & purification; D010281:Parathyroid Hormone / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014808:Vitamin D Deficiency / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology
D007527:Isoenzymes; D010281:Parathyroid Hormone; D009218:Myosins; D002117:Calcitriol; D002118:Calcium