Proton leak exerts stronger control over ATP/ADP in mitochondria from clonal pancreatic beta-cells (INS-1E) than in those from rat skeletal muscle, due to the higher proton conductance of INS-1E mitochondria [Affourtit and Brand (2006) Biochem. J. 393, 151-159]. In the present study, we demonstrate that high proton leak manifests itself at the cellular level too: the leak rate (measured as myxo...

AIMS Rupture-prone atherosclerotic plaques show an elevated temperature, but a molecular explanation for this phenomenon is unknown. Here, we investigated whether mitochondrial uncoupling protein 2 (UCP2) could be involved because this protein is a macrophage homologue of thermogenin in brown fat tissue. METHODS AND RESULTS Immunohistochemistry, western blotting, and real-time quantitative po...

To investigate the expression of miR-30e-UCP2 pathway in different stages of alcoholic liver disease (ALD) and its capacity and mechanism in regulating alcoholic hepatitis (AH) progress. C57BL/6 mice were fed with Lieber-DeCaril (LD) diet for 4 and 12 weeks to establish models of alcoholic fat infiltration (AFI) and AH. Based on AFI feeding, the alcoholic hepatic fibrosis (AHF) was set up with ...

Uncoupling protein-2 (UCP2) is a mitochondrial inner-membrane carrier protein that is involved in the control of fatty acid metabolism. To understand the mechanism of the transcriptional regulation of ucp2 in the pathogenesis of nonalcoholic steatohepatitis (NASH), we cloned 500 bp upstream of the ucp2 exon 1 from a rat liver cDNA library and identified cis-acting regulatory elements. The trans...

BACKGROUND We have shown the involvement of mitochondrial uncoupling protein-2 (UCP2) in the cytotoxicity by N-methyl-D-aspartate receptor (NMDAR) through a mechanism relevant to the increased mitochondrial Ca(2+) levels in HEK293 cells with acquired NMDAR channels. Here, we evaluated pharmacological profiles of ethanol on the NMDA-induced increase in mitochondrial Ca(2+) levels in cultured mur...

Uncoupling protein 2 (UCP2) regulates the production of mitochondrial reactive oxygen species (ROS) and cellular energy transduction under physiological or pathological conditions. In this study, we aimed to determine whether mitochondrial UCP2 plays a protective role in cardiomyocytes under septic conditions. In order to mimic the septic condition, rat embryonic cardiomyoblast-derived H9C2 cel...

Reactive oxygen species (ROS) have been implicated in the pathogenesis of acute pancreatitis (AP) for many years but experimental evidence is still limited. Uncoupling protein 2 (UCP2)-deficient mice are an accepted model of age-related oxidative stress. Here, we have analysed how UCP2 deficiency affects the severity of experimental AP in young and older mice (3 and 12 months old, respectively)...

Limited information is available regarding mechanisms that link the known carcinogenic risk factors of gastro-esophageal reflux and cigarette smoking to metabolic alterations in esophageal adenocarcinoma (EAC). In the present study, we utilized a novel in-vitro model to examine whether bile acid and cigarette smoke increase the aggressiveness of EAC and whether these changes are associated with...

Research on brown adipose tissue and its hallmark protein, mitochondrial uncoupling protein UCP1, has been conducted for half a century and has been traditionally studied in the Institute of Physiology (AS CR, Prague), likewise UCP2 residing in multiple tissues for the last two decades. Our group has significantly contributed to the elucidation of UCP uncoupling mechanism, fully dependent on fr...

Vascular dysfunction in response to reactive oxygen species (ROS) plays an important role in the development and progression of atherosclerotic lesions. In most cells, mitochondria are the major source of cellular ROS during aerobic respiration. Under most conditions the rates of ROS formation and elimination are balanced through mechanisms that sense relative ROS levels. However, a chronic imb...