BACKGROUND Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage by a non-prostaglandin (PG) dependent "topical" action and by inhibiting cyclooxygenase. AIMS To discriminate between these two effects by studying some key pathophysiological steps in NSAID enteropathy following administration of (R)- and (S)-flurbiprofen, the racemic mixture, and an uncoupler, dinitrophe...

Defects in mitochondrial function have been shown to participate in the induction of neuronal cell injury. The aim of the present study was to assess the preventive effect of licorice compounds glycyrrhizin and 18beta-glycyrrhetinic acid against the toxicity of parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP+) in relation to the mitochondria-mediated cell death process and role of oxid...

The permeability transition (PT) denotes an increase of the mitochondrial inner membrane permeability to solutes with molecular masses up to about 1500 Da. It is presumed to be mediated by opening of a channel, the permeability transition pore (PTP), whose molecular nature remains a mystery. Here I briefly review the history of the PTP, discuss existing models, and present our new results indic...

The 'mitochondrial permeability transition', characterized by a sudden induced change of the inner mitochondrial membrane permeability for water as well as for small substances (</=1.5 kDa), has been known for three decades. Research interest in the entity responsible for this phenomenon, the 'mitochondrial permeability transition pore' (mPTP), has dramatically increased after demonstration tha...

The molecular mechanisms underlying the initiation and control of the release of cytochrome c during mitochondrion-dependent apoptosis are thought to involve the phosphorylation of mitochondrial Bcl-2 and Bcl-x(L). Although the c-Jun N-terminal kinase (JNK) has been proposed to mediate the phosphorylation of Bcl-2/Bcl-x(L) the mechanisms linking the modification of these proteins and the releas...

There is solid evidence that a sudden change in mitochondrial membrane permeability (mitochondrial permeability transition, MPT) plays a critical role in reperfusion-induced myocardial necrosis. We hypothesized that sarcoplasmic reticulum (SR) Ca(2+) cycling may induce partial MPT in microdomains of close anatomic proximity between mitochondria and SR, resulting in hypercontracture and cell dea...

Mitochondrial ion transport, oxidative phosphorylation, redox balance, and physical integrity are key factors in tissue survival following potentially damaging conditions such as ischemia/reperfusion. Recent research has demonstrated that pharmacologically activated inner mitochondrial membrane ATP-sensitive K+ channels (mitoK(ATP)) are strongly cardioprotective under these conditions. Furtherm...

OBJECTIVE The aim of this study was to determine the in vitro effect of glutamine and insulin on apoptosis, mitochondrial membrane potential, cell permeability, and inflammatory cytokines in hyperglycemic umbilical vein endothelial cells. MATERIALS AND METHODS Human umbilical vein endothelial cells were grown and subjected to glutamine and insulin to examine the effects of these agents on the...