Ca 2+ -regulatory muscle proteins in the alcohol-fed rat

Abstract

Alcoholic myopathy is characterized by muscle weakness and difficulties in gait and locomotion. It is one of the most prevalent skeletal muscle disorders in the Western hemisphere, affecting between 40% and 60% of all chronic alcohol misusers. However, the pathogenic mechanisms are unknown, although recent studies have suggested that membrane defects occur as a consequence of chronic alcohol exposure. It was our hypothesis that alcohol ingestion perturbs membranelocated proteins associated with intracellular signalling and contractility, in particular those relating to calcium homeostasis. To test this, we fed male Wistar rats nutritionally complete liquid diets containing ethanol as 35% of total dietary energy. Controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. At the end of 6 weeks, rats were killed and skeletal muscles dissected. These were used to determine important ion-regulatory skeletal muscle proteins including sarcalumenin (SAR), sarcoplasmic-endoplasmic reticulum Ca 2؉ -adenosine triphosphatase (ATPase) (SERCA1), the junctional face protein of 90 kd (90-JFP), ␣ 1 -and ␣ 2 -dihydropyridine receptor (␣ 1 -DHPR and ␣ 2 -DHPR), and calsequestrin (CSQ) by immunoblotting. The relative abundance of microsomal proteins was determined by immunoblotting using the enhanced chemiluminescence (ECL) technique. The data showed that alcohol-feeding significantly reduced gastrocnemius and hind limb muscle weights (P < .05 in both instances). Concomitant changes included increases in the relative amounts of SERCA1 (P < .05) and Ca 2؉ -ATPase activity (P < .025). However, there were no statistically significant changes in either SAR, 90-JFP, ␣ 1 -DHPR or ␣ 2 -DHPR (P > .2 in all instances). Reductions in CSQ were of marginal significance (P ‫؍‬ .0950). We conclude that upregulation of SERCA1 protein and Ca 2؉ -ATPase activity may be an adaptive mechanism and/or a contributory process in the pathology of alcohol-induced muscle disease.

Biphasic changes in cardiac excitation-contraction coupling early in chronic alcohol exposure

“…However, previous reports regarding chronic EtOH effects on sarco(endo)plasmic reticulum Ca 2ϩ -ATPases (SERCA) collectively suggest similar transitory changes. It has been reported that increased skeletal muscle (SERCA1) protein expression and ATPase activity occur after 6 wk of chronic EtOH exposure (38), and this is accompanied by a reported increase in cardiac SERCA2 activity after 10 wk of chronic EtOH exposure (17). Conversely, SERCA2 protein expression has been reported to be unchanged after 7 mo of chronic EtOH exposure (11), and SR Ca 2ϩ binding and uptake have been reported to be inhibited after 3 mo of chronic EtOH exposure (41).…”

Fingerprint Profile of Alcohol‐Associated Heart Failure in Human Hearts

“…According to recommendations from the National Institute of Alcohol Abuse and Alcoholism’s and the National Heart, Lung and Blood Institute’s sponsored workshop on “Alcohol and the Cardiovascular System: Research Challenges and Opportunities”, 2 key conclusions were made: (i) studies were needed to determine genes de‐regulated in order to assess mechanisms and (ii) pharmacogenomics is needed in determining effective treatment (Lucas et al., 2005). These conclusions were drawn from the fact that excessive alcohol intake results in cardiomyopathy in 15 to 35% of alcoholics, which is thought to account for about half of all cases of heart failure in Western countries (Ohlendieck et al., 2003; Preedy et al., 2003). In addition, alcohol abuse, despite being a major health problem, remains poorly researched and understood in relation to gene regulation and the development of heart failure.…”

Зміна швидкісно-силових параметрів скорочення musculus soleus щурів при хронічній алкоголізації

“…Надмірна активація процесів вільнорадикального перекисного окиснення спричинює каскад негативних біохімічних реакцій і патологічних змін, які лежать в основі багатьох захворювань людини й тварин, зокрема атеросклерозу, ішемічної хвороби серця, діабетичної ангіопатії, нейродегенеративних та аутоімунних захворювань, раку, променевої хвороби, псоріазу, опіків, катаракти й ін. [5,6]. В ізометричних умовах скорочення м'яза аналіз реєстрованого зусилля, що розвивається м'язом при частотно-модульованій стимуляції її нерва, є якісним показником рівня нейро-й мітопатичних патологічних процесів.…”