Chronic dietary Mg2+ deficiency induces cardiac apoptosis in the rat heart.
Severe Mg2+ deficiency provokes pro-oxidative and pro-inflammatory changes, and also has been shown to be pro-apoptotic in thymus and certain cell cultures. In this study we examined the extent that chronic severe dietary Mg2+ deficiency induces apoptosis in the heart. Sprague-Dawley rats were fed during three weeks with normal (25 mM, Mg-control) or magnesium deficient (2.25 mM, Mg-deficient) diets, after which, hearts were harvested and frozen. DNA fragmentation was examined in heart tissue sections, and while < 1% of nuclei were positive for apoptosis in Mg-control rat tissue, over 32% of nuclei gave positive for Klenow fragments in hearts from Mg-deficient rats. Caspase 3 activity measurements in heart homogenates showed a 3.9-fold increase in enzyme activity in Mg-deficient rat hearts compared to Mg-controls (p < 0.002); and furthermore, western blot analysis of cleaved PARP (caspase 3 substrate), showed a 4.6-fold increase of cleaved PARP in Mg-deficient rat hearts (p < 0.002). In summary, our data indicate that chronic Mg2+ deficiency induces apoptosis of myocardium in vivo.
Tejero-Taldo
M Isabel
MI
Division of Experimental Medicine, Department of Biochemistry & Molecular Biology, The George Washington University Medical Center, 2300 IST, NW. Washington, D.C. 20037, USA. phymit@gwumc.edu
Chmielinska
Joanna J
JJ
Weglicki
William B
WB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002908:Chronic Disease; D053938:DNA Fragmentation / Q000187:drug effects; D019587:Dietary Supplements; D006321:Heart / Q000187:drug effects*; D008274:Magnesium / Q000008:administration & dosage* / Q000378:metabolism; D008275:Magnesium Deficiency / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D008274:Magnesium