Dysfunction of SERCA pumps as novel mechanism of methylglyoxal cytotoxicity.

A novel pathway of methylglyoxal (MGX)-induced apoptosis via sarcoplasmic reticulum Ca-ATPase (SERCA) is presented. Interaction of SERCA1 with MGX was investigated by molecular docking and experimentally in a cell-free system. MGX concentration- and time-dependently decreased SERCA1 activity.

Pycnogenol Cytotoxicity in Pancreatic INS-1E β cells Induced by Calcium Dysregulation.

Natural standardized flavonoid extract from the bark of Pinus pinaster, Pycnogenol (Pyc), was recently found to decrease intensively the activity of sarcoplasmic reticulum Ca -ATPase of rabbit skeletal muscle (SERCA1). On the basis of this inhibitory effect in a cell-free system and similarities of SERCA1 to its other isoforms, proapoptotic properties of Pyc may be expected in cellular systems. Pycnogenol (40-100 μg/mL) induced a concentration-dependent decrease of the viability of pancreatic INS-1E β cells associated with induction of apoptosis.

Novel quercetin derivatives: From redox properties to promising treatment of oxidative stress related diseases.

A set of O-substituted quercetin derivatives was prepared with the aim to optimize bioavailability and redox properties of quercetin, a known agent with multiple health beneficial effects. Electron-acceptor/-donor properties of the agents were evaluated theoretically by quantum chemical calculations and by experimental methods in cell-free model systems (2,2-diphenyl-1-picrylhydrazyl (DPPH) test, the ferric reducing ability of plasma (FRAP), peroxynitrite scavenging, protein-thiol oxidation) and in cellular systems of fibroblasts, microglials and cancer lines. The order of individual antioxidant effects varied dependently on the system used.

Rutin stimulates sarcoplasmic reticulum Ca(2+)-ATPase activity (SERCA1) and protects SERCA1 from peroxynitrite mediated injury.

In this study we analyzed the protective action of the flavonoid rutin on peroxynitrite (ONOO(-)) mediated impairment of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA1 isoform), especially related to posttranslational and conformational changes. Rutin concentration dependently protected ONOO(-) induced SERCA1 activity decrease with effective concentration EC50 of 18 ± 1.5 µM.

Modulation of rabbit muscle sarcoplasmic reticulum Ca(2+)-ATPase activity by novel quercetin derivatives.

Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) is the pump crucial for calcium homeostasis and its impairment results in pathologies such as myopathy, heart failure or diabetes. Modulation of SERCA activity may represent an approach to the therapy of diseases with SERCA impairment involvment. Quercetin is flavonoid known to modulate SERCA activity.

Novel quercetin derivatives in treatment of peroxynitrite-oxidized SERCA1.

Sarco/endoplasmic reticulum calcium ATP-ase (SERCA) is regulated by low concentrations of peroxynitrite and inhibited by high levels, as indicated in human diseases. We studied quercetin (Q) and its novel derivatives monochloropivaloylquercetin (MPQ) and chloronaphthoquinonequercetin (CHQ) as agents with expected preventive properties against peroxynitrite-induced SERCA impairment. Q and MPQ protected the SERCA1 against peroxynitrite induced activity decrease, while CHQ potentiated the inhibitory effect of peroxynitrite.

Sarcoplasmic reticulum Ca2+-ATPase from rabbit skeletal muscle modified by peroxynitrite.

Objective: Effect of peroxynitrite on SERCA1 activity was studied in correlation with enzyme carbonylation. Kinetic parameters and location of peroxynitrite effect on SERCA1 were determined.

Methods: Carbonyls were determined by immunoblotting.

Effects of novel quercetin derivatives on sarco/endoplasmic reticulum Ca2+-ATPase activity.

Objectives: We examined effect of novel quercetin derivatives on sarcoplasmic reticulum (SR) Ca-ATPase activity isolated from skeletal muscles and their potential to prevent injury of SERCA induced by peroxynitrite that is elevated in multiple pathological processes.

Methods: SR was isolated by ultracentrifugation, ATPase activity of SERCA was measured by NADH-coupled enzyme assay. Sulfhydryl and carbonyl groups content was determined to test oxidation of SERCA.

Modulation of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase activity and oxidative modification during the development of adjuvant arthritis.

Adjuvant arthritis (AA) was induced by intradermal administration of Mycobacterium butyricum to the tail of Lewis rats. In sarcoplasmic reticulum (SR) of skeletal muscles, we investigated the development of AA. SR Ca(2+)-ATPase (SERCA) activity decreased on day 21, suggesting possible conformational changes in the transmembrane part of the enzyme, especially at the site of the calcium binding transmembrane part.

Pycnogenol and Ginkgo biloba extract: effect on peroxynitrite-oxidized sarcoplasmic reticulum Ca-ATPase.

The effect of two natural standardized plant extracts, Pycnogenol(®) and EGb 761, on sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) activity and posttranslational modifications induced by peroxynitrite was investigated to assess their possible protective role. EGb 761 was found to have a protective effect on SERCA activity in the concentration range of 5-40 µg/ml. On the other hand, Pycnogenol(®) caused a decrease of SERCA activity at concentrations of 25 µg/ml.