Severe food restriction induces myocardial dysfunction related to SERCA2 activity.
Previous studies have shown that food restriction promotes myocardial dysfunction in rats. However, the molecular mechanisms that are responsible are unclear. We investigated the role of sarcoplasmic reticulum Ca2+-ATPase (SERCA2) on myocardial performance in food-restricted rats. Male Wistar-Kyoto rats, 60 days old, were fed a control or restricted diet (daily energy intake reduced to 50% of the control) for 90 days. Expression of Serca2a, phospholamban (PLB), Na+/Ca2+ exchanger (NCX), and thyroid hormone receptor (TRalpha1, TRbeta1) mRNA was determined by quantitative PCR. SERCA2 activity was measured by using 20 micromol/L cyclopiazonic acid (CPA) in a left ventricular papillary muscle preparation during isometric contraction in basal conditions and during post-rest contraction. Serum concentrations of thyroxine (T4) and thyrotropin (TSH) were also determined. The 50%-restricted diet reduced body and ventricular weight and serum T4 and TSH levels. The interaction of CPA and food restriction reduced peak developed tension and maximum rate of tension decline (-dT/dt), but increased the resting tension intensity response during post-rest contraction. PLB and NCX mRNA were upregulated and TRalpha1 mRNA was downregulated by food restriction. These results suggest that food restriction promotes myocardial dysfunction related to impairment of sarcoplasmic reticulum Ca2+ uptake as a result of a hypothyroid state.
Department of Clinical and Cardiology, School of Medicine, UNESP State University Júlio Mesquita Filho, Botucatu, São Paulo, Brazil.
Mário Mateus
MM
Sugizaki
André Soares
AS
Leopoldo
Marina Politi
MP
Okoshi
Alessandro
A
Bruno
Sandro José
SJ
Conde
Ana Paula
AP
Lima-Leopoldo
Carlos Roberto
CR
Padovani
Robson Francisco
RF
Carvalho
André Ferreira
AF
do Nascimento
Dijon Henrique Salomé
DH
de Campos
Célia Regina
CR
Nogueira
Antonio Carlos
AC
Cicogna
D000818:Animals; D002118:Calcium / Q000378:metabolism; D031204:Caloric Restriction / Q000009:adverse effects*; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism*; D005508:Food Deprivation; D006352:Heart Ventricles / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D010210:Papillary Muscles / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011921:Rats, Inbred WKY; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D037021:Thyroid Hormone Receptors alpha / Q000096:biosynthesis; D037042:Thyroid Hormone Receptors beta / Q000096:biosynthesis; D013963:Thyroid Hormones / Q000097:blood
C506948:Atp2a2 protein, rat; D012333:RNA, Messenger; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium