We recently developed a clinically relevant mini-swine model of heart failure with preserved ejection fraction (HFpEF), in which diastolic dysfunction was associated with increased mitochondrial permeability transition (MPT). Early diastolic function is ATP and Ca(2+)-dependent, thus, we hypothesized chronic low doses of cyclosporine (CsA) would preserve mitochondrial function via inhibition of...

PURPOSE Glutathione (GSH) plays a key role in protection against oxidative stress. L-cysteine is thought to be rate-limiting for the synthesis of glutathione (GSH) and therefore may be a critical component in protection against oxidative stress. The purpose of this study was to investigate the role of L-cysteine in GSH metabolism and oxidative stress in human retinal pigment epithelial (hRPE) c...

In animal models of neurodegenerative diseases pathological changes vary with the type of organ and species of the animals. We studied differences in the mitochondrial permeability transition (mPT) and reactive oxygen species (ROS) generation in the liver (LM) and brain (BM) of Sprague-Dawley rats and C57Bl mice. In the presence of ADP mouse LM and rat LM required three times less Ca(2+) to ini...

Chondrocyte apoptosis has been recognized as an important factor in the pathogenesis of osteoarthritis (OA). Hydrogen peroxide (H2O2), which produces reactive oxygen species, reportedly induces apoptosis in chondrocytes. The ginsenoside Rb1 (GRb1) is the principal component in ginseng and has been shown to have a variety of biological activities, such as anti-arthritis, anti-inflammation, and a...

Objective: Extracts of Anchomanes difformis (AD) are used in folkloric medicine to treat several diseases and infections. However, their roles in mitochondrial permeability transition pore opening are not known. Material and Methods: The viability of mitochondria isolated from Wistar rat liver used in this experiment, was assessed by monitoring their swel...

Although information about the mechanism of apoptosis is rapidly increasing, critical roles of mitochondria in the regulation of cell death remain to be elucidated. Recent studies revealed that reactive oxygen species (ROS) in cells increase prior to the onset of DNA fragmentation, a late phase event in apoptosis. An overload of Ca 2 induces a classic type of membrane permeability transition (C...

Mitochondrial permeability transition (MPT) pores have recently been implicated as a potential mediator of myocardial ischemic injury. Nitric oxide (NO) donors induce a powerful late phase of cardioprotection against ischemia-reperfusion injury; however, the cellular mechanisms involved are poorly understood. The role of MPT pores as a target of cardioprotective signaling pathways activated by ...

Freshly isolated mouse hepatocytes were used to determine the role of mitochondrial permeability transition (MPT) in acetaminophen (APAP) toxicity. Incubation of APAP (1 mM) with hepatocytes resulted in cell death as indicated by increased alanine aminotransferase in the media and propidium iodide fluorescence. To separate metabolic events from later events in toxicity, hepatocytes were preincu...

BACKGROUND Eosinophils are critically involved in the pathogenesis of asthma. Nitric oxide (NO) is produced in high amounts in asthmatic lungs and has an important role as a regulator of lung inflammation. NO was previously shown to induce eosinophil apoptosis mediated via c-jun N-terminal kinase (JNK) and caspases. Our aim was to clarify the cascade of events leading to NO-induced apoptosis in...