Cardiac sarcoplasmic reticulum Ca²⁺-ATPase: heat production and phospholamban alterations promoted by cold exposure and thyroid hormone

Abstract

Ketzer LA, Arruda AP, Carvalho DP, de Meis L. Cardiac sarcoplasmic reticulum Ca 2ϩ -ATPase: heat production and phospholamban alterations promoted by cold exposure and thyroid hormone. Am J Physiol Heart Circ Physiol 297: H556 -H563, 2009. First published June 12, 2009 doi:10.1152/ajpheart.00302.2009.-Shortterm response to cold promotes a small but significant rise in serum T3 in euthyroid rabbits, where the heart is an important target of T3 action. In this work, we measured changes in sarco(endo)plasmic reticulum Ca 2ϩ -ATPase (SERCA2a) and phospholamban (PLB) in hearts of hypo-and hyperthyroid rabbits and compared them with modifications induced by short-and long-term cold exposure. Shortterm cold exposure promotes a small increase in T3 and, similar to hyperthyroidism, induces an increase of heart SERCA2a expression. The total PLB content does not change in hyperthyroidism, but short-term cold exposure promotes a significant decrease in total PLB and an increase in the ratio between phosphorylated and total PLB. The temperature of a given tissue depends on the balance between the heat provided by blood circulation and the rate of heat production by the tissue. In an attempt to evaluate the heat contribution of cardiac tissue, we measured mitochondrial respiration in permeabilized cardiac muscle and heat produced by cardiac sarcoplasmic reticulum (SR) during Ca 2ϩ transport. We observed that there was an increase in oxygen consumption and heat production during Ca 2ϩ transport by cardiac SR in both hyperthyroidism and short-term cold exposure. In contrast, both the mitochondrial respiration rate and heat derived from Ca 2ϩ transport were decreased in hypothyroid rabbits. The heart changes in oxygen consumption, SERCA2a-PLB ratio, and Ca 2ϩ -ATPase activity detected during short-term cold exposure were abolished after cold adaptation. We hypothesize that the transient rise in serum T3 contributes to the short-term response to cold exposure. heart; calcium adenosinetriphosphatase; thermogenesis; mitochondrial respiration THYROID HORMONE significantly affects the cardiovascular system, producing profound changes in cardiac contractility, cardiac output, blood pressure, and myocardial oxygen consumption (9, 30). The mechanisms underlying these changes involve direct gene transcriptional regulation induced by thyroid hormone, which, in turn, affects the excitation-contraction coupling by modifying both the cytosolic Ca 2ϩ cycling (33, 50, 55) and myofilament expression (25, 36). Furthermore, thyroid hormone alters energetic metabolism in the myocardium (48) and interacts with the sympathetic nervous system (SNS) by increasing adrenergic receptor function and/or density (4, 52).The sarco(endo)plasmic reticulum Ca 2ϩ -ATPase (SERCA) plays a central role in the coupling of contraction and relaxation in the myocardium. This enzyme transports Ca 2ϩ inside the SR lumen by using ATP hydrolysis as an energy source (19,26,28). In addition to being important for muscle contraction, SERCA is one of the heat sources contribu...

Is Subclinical Hypothyroidism a Cardiovascular Risk Factor in the Elderly?

“…In most patients, CV changes are reversible when the underlying thyroid function failure is recognized and treated (47, 54 -56). To understand better the impact of hypothyroidism on the CV system, it is necessary to take into account the molecular effects of thyroid hormones and the modifications that they exert at the tissue level (57)(58)(59). The complex interaction of T 3 with myocardium clearly explains the early cardiac diastolic impairment and prolonged isovolumic relaxation phase of hypothyroid patients (51,54).…”

Thyroid hormone regulates cardiac performance during cold acclimation in Zebrafish (Danio rerio)

“…These results indicate that TH influences SERCA activity in zebrafish via post-transcriptional mechanisms, possibly through the allosteric regulation of phospholamban. In the mammalian heart, TH is known to increase the fraction of phosphorylated (non-inhibitory) relative to nonphosphorylated (inhibitory) phospholamban (Carr and Kranias, 2002;Ketzer et al, 2009), in addition to controlling the transcriptional expression of phospholamban. Thus, our working hypothesis here is that TH regulates the phosphorylation state of phospholamban to increase SERCA activity in the absence of changes to overall SERCA and phospholamban mRNA levels.…”

“…However, TH does determine cardiac function in mammals. For instance, in mammals TH increases the expression and activity of proteins involved in calcium cycling through both genomic (transcriptional) and non-genomic pathways (Kahaly and Dillmann, 2005;Ketzer et al, 2009). TH is a transcriptional regulator of SERCA and its inhibitor phospholamban (Carr and Kranias, 2002).…”

Antioxidant and antitumor activities of Capparis spinosa L. and the related mechanisms

“…The activity of Na + K + -ATPase and Ca 2+ -ATPase was reduced in the DOX group, while DOX initiated membrane lipid peroxidation (41). MDA is the metabolite of lipid peroxidation products, which could interfere with metabolic to cellular acidosis.…”