Protein phosphatase 1 (PP1) is a key regulator of important cardiac signaling pathways. Dysregulation of PP1 has been heavily implicated in cardiac dysfunctions. Accordingly, pharmacological targeting of PP1 activity is considered for therapeutic intervention in human cardiomyopathies. Recent evidence from animal models implicated previously unrecognized, isoform-specific activities of PP1 in the healthy and diseased heart. Therefore, this study examined the expression of the distinct PP1 isoforms PP1α, β, and γ in human heart failure (HF) and atrial fibrillation (AF) and addressed the consequences of β-adrenoceptor blocker (beta-blocker) therapy for HF patients with reduced ejection fraction on PP1 isoform expression. Using western blot analysis, we found greater abundance of PP1 isoforms α and γ but unaltered PP1β levels in left ventricular myocardial tissues from HF patients as compared to non-failing controls. However, expression of all three PP1 isoforms was higher in atrial appendages from patients with AF compared to patients with sinus rhythm. Moreover, we found that in human failing ventricles, beta-blocker therapy was associated with lower PP1α abundance and activity, as indicated by higher phosphorylation of the PP1α-specific substrate eIF2α. Greater eIF2α phosphorylation is a known repressor of protein translation, and accordingly, we found lower levels of the endoplasmic reticulum (ER) stress marker Grp78 in the very same samples. We propose that isoform-specific targeting of PP1α activity may be a novel and innovative therapeutic strategy for the treatment of human cardiac diseases by reducing ER stress conditions.
An improved high-performance thin-layer chromatographic (HPTLC) method has been developed for quantitative analysis of stratum corneum lipids. When used for quantification of in-vivo-extracted skin lipids, the optimized method resulted in improved separation of cholesterol, cholesteryl esters, free fatty acids, and squalene. Variation in repeatability for cholesterol, cholesteryl esters and free fatty acids was under ±5%. The extraction recovery was 91.4 ± 1.2% (mean ± CV). Coefficients of variation ranged from 0.8 to 3.8%. The limits of detection S/N 3:1 and of quantification S/N 5:1 under the given conditions were: cholesteryl sulfate 12.5/25 ng, ceramide [AP] D-compound 50/250 ng, ceramide [NP] 50/125 ng, ceramide [NS] 125/250 ng, cholesterol 50/125 ng, palmitic acid 50/250 ng, and cholesteryl oleate 50/125 ng.
Unfortunately, the author name Samuel Sossalla contained a typing error in the original publication. The original article has been corrected. We apologize for any inconvenience caused.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.