Thiol/disulfide status regulates the activity of thiol-containing kinases related to energy homeostasis in rat kidney

Abstract

Considering that thiol-containing enzymes like kinases are critical for several metabolic pathways and energy homeostasis, we investigated the effects of cystine dimethyl ester and/or cysteamine administration on kinases crucial for energy metabolism in the kidney of Wistar rats. Animals were injected twice a day with 1.6 µmol/g body weight cystine dimethyl ester and/or 0.26 µmol/g body weight cysteamine from the 16 th to the 20 th postpartum day and euthanized after 12 hours. Pyruvate kinase, adenylate kinase, creatine kinase activities and thiol/disulfide ratio were determined. Cystine dimethyl ester administration reduced thiol/disulfide ratio and inhibited the kinases activities. Cysteamine administration increased the thiol/ disulfide ratio and co-administration with cystine dimethyl ester prevented the inhibition of the enzymes. Regression between the thiol/disulfide ratio, and the kinases activities were significant. These results suggest that redox status may regulate energy metabolism in the rat kidney. If thiol-containing enzymes inhibition and oxidative stress occur in patients with cystinosis, it is possible that lysosomal cystine depletion may not be the only beneficial effect of cysteamine administration, but also its antioxidant and thiol-protector effect.

Relaxin Inhibits Ventricular Arrhythmia and Asystole in Rats With Pulmonary Arterial Hypertension

“…CVs in the RVs of the RLX LD group were slower than in the RV of the RLX HD group ( p = 0.02), whereas there was a trend toward slower CVs in the LVs ( p = 0.09). These data are consistent with previous findings in atria and ventricles ( 12 , 13 , 19 ) and show that RLX increases CVs in a dose-dependent manner.…”

“…The redox state of the cytosolic milieu is in a reduced thiol state in physiological conditions and metabolic energy is required to maintained a reduced milieu. A spectrum of cysteines in various peptides can be oxidized resulting in a loss of enzymatic function [e.g., creatine kinase, SERCA, ( 19 , 20 )] or modulation of ion channels [e.g., L-type Ca 2+ channels ( 21 ) and SR Ca 2+ release channels or ryanodine receptors (RyR) ( 22 )]. The cardiac Ryanodine receptor, RyR2 is particularly sensitive to thiol oxidation and has been shown to contain “critical” or “hyperreactive” thiols which when oxidized and reduced, open and close the channel, respectively ( 23 ).…”

Nanocapsules With Naringin And Naringenin Affect Hepatic and Renal Energy Metabolism Without Altering Serum Markers of Toxicity in Rats

“…A very important enzyme for maintaining cell viability is PK, this enzyme plays a very important role in glycolysis, the main way of obtaining energy from renal and hepatic cells, where it catalyzes the dephosphorylation of phosphoenolpyruvate (PEP) in pyruvate, generating two molecules of ATP by glucose (Shuch et al 2013). So that the inhibition of the PK is related with decrease intracellular levels of ATP so result damage in the cell viability, in addition the oxidative stress can cause decrease PK due to pyruvate is an antioxidant endogenous molecule, this a very important for the cell homeostasis (Baldissera et al 2015;Rech et al 2017). Adenylate kinase (AK), CK and PK are key enzymes for balance the homeostasis energy.…”