Down-regulation of the cardiac sarcoplasmic reticulum ryanodine channel in severely food-restricted rats

Abstract

We have shown that myocardial dysfunction induced by food restriction is related to calcium handling. Although cardiac function is depressed in food-restricted animals, there is limited information about the molecular mechanisms that lead to this abnormality. The present study evaluated the effects of food restriction on calcium cycling, focusing on sarcoplasmic Ca 2+ -ATPase (SERCA2), phospholamban (PLB), and ryanodine channel (RYR2) mRNA expressions in rat myocardium. Male Wistar-Kyoto rats, 60 days old, were submitted to ad libitum feeding (control rats) or 50% diet restriction for 90 days. The levels of left ventricle SERCA2, PLB, and RYR2 were measured using semi-quantitative RT-PCR. Body and ventricular weights were reduced in 50% food-restricted animals. RYR2 mRNA was significantly decreased in the left ventricle of the foodrestricted group (control = 5.92 ± 0.48 vs food-restricted group = 4.84 ± 0.33, P < 0.01). The levels of SERCA2 and PLB mRNA were similar between groups (control = 8.38 ± 0.44 vs food-restricted group = 7.96 ± 0.45, and control = 1.52 ± 0.06 vs food-restricted group = 1.53 ± 0.10, respectively). Down-regulation of RYR2 mRNA expressions suggests that chronic food restriction promotes abnormalities in sarcoplasmic reticulum Ca 2+ release. Key wordsFood restriction induces beneficial health effects such as increased longevity and retards or prevents a broad spectrum of agerelated pathophysiological changes such as loss of skeletal muscle mass, diabetes mellitus, hypertension, and cancer (1-3). Recent research from our laboratory has shown that 50% food restriction promotes left ventricular dysfunction and increases contraction and relaxation times in isolated papillary muscle of both young Wistar-Kyoto normotensive and spontaneously hypertensive rats (4-7). Sugizaki et al. (7) observed that myocardial dysfunction in food-restricted rats is related to calcium handling. However, these investigators were unable to identify calcium handling site abnormalities.Few studies have analyzed the molecular

Basal and �-Adrenergic Cardiomyocytes Contractility Dysfunction Induced by Dietary Protein Restriction is Associated with Downregulation of SERCA2a Expression and Disturbance of Endoplasmic Reticulum Ca2+Regulation in Rats

“…These results indicate that low protein dietary intake can modify the function of RyR2. Other researchers, working with different animal models of cardiac dysfunction, also found similar results to those found in this study [22,24]. …”

“…The abnormal activity of RyR2 has been shown in different types of heart disease [22,24,25,26]. A common feature in most models of experimental heart failure is the decline of the Ca 2+ content of the sarcoplasmic reticulum.…”

Protein Restriction after Weaning Modifies the Calcium Kinetics and Induces Cardiomyocyte Contractile Dysfunction in Rats

“…Thus, a downregulation in the expression or function of SERCA2 and PLB can be directly linked to the prolonged relaxation time of cell contraction and calcium transient decay time, as evidenced here in protein-restricted rats. Although food restriction did not change the levels of LV SERCA2 and PLB mRNAs in rats [Vizotto et al, 2007], it decreased the SR Ca 2+ uptake activity in the rat myocardium [Rupp et al, 1997].…”

“…Thus, this analysis indicates that PR prevents functional adaptations of these regulatory proteins to compensate for deficits in intracellular calcium kinetics, which is an event that is essential for optimal cell mechanical behavior. Indeed, food restriction has been shown to diminish the protein content of L-type Ca 2+ channels [De Tomasi et al, 2009] and the expression and activity of RyR2 receptors in the LV of rats, adaptations involved in intracellular Ca 2+ kinetics dysfunction and, consequently, reduced force and velocity of cell contraction [O'Brien et al, 1995;Vizotto et al, 2007].…”

Exercício e restrição alimentar aumentam o RNAm de proteínas do trânsito de Ca2+ miocárdico em ratos

“…Molecular structures found in the sarcolemma, slow L-type calcium channel (L-channel) and sodium/potassium exchanger (NCX), also found in the sarcoplasmic reticulum, ryanodine channel, the calsequestrin (CQS), the sarcoplasmic reticulum calcium pump (SERCA2a) and phospholamban, are involved in the intracellular calcium handling and participate in the cardiac muscle contraction and relaxation 11 . Studies show that FR decreases the gene expression of ryanodine 12 , SERCA2 13 , L-channel 14 , while physical training (PT) increases the mRNA of SERCA2 [15][16][17] , ryanodine 18,19 and L-channel 20 . The transcription of the molecular structures involved in the intracellular calcium handling can be modulated by thyroid hormones (TH), via nuclear receptors of HT [21][22][23] .…”