Lemasters, John J. Mechanisms of Hepatic Toxicity. V. Necrapoptosis and the mitochondrial permeability transition: shared pathways to necrosis and apoptosis. Am. J. Physiol. 276 (Gastrointest. Liver Physiol. 39): G1–G6, 1999.—Opening of a high-conductance pore conducting solutes of molecular mass ,1,500 Da causes onset of the mitochondrial permeability transition (MPT). Cyclosporin A blocks thi...

The mid-Pleistocene transition (MPT) marked a fundamental change in glacial-interglacial periodicity, when it increased from ~41-thousand-year to 100-thousand-year cycles and developed higher-amplitude climate variability without substantial changes in the Milankovitch forcing. Here, we document, by using Nd isotopes, a major disruption of the ocean thermohaline circulation (THC) system during ...

The combination of melphalan-prednisone-thalidomide (MPT) has been investigated in several clinical studies that differed significantly with regard to patient characteristics and treatment schedules. This prospective trial differs from previous melphalan-prednisone (MP) vs. MPT trials by treatment dosing, duration, routine anticoagulation, and permission for a crossover. Newly diagnosed patient...

Onset of the mitochondrial permeability transition (MPT) is the penultimate event leading to lethal cellular ischemia-reperfusion injury, but the mechanisms precipitating the MPT after reperfusion remain unclear. Here, we investigated the role of mitochondrial free Ca(2+) and reactive oxygen species (ROS) in pH- and MPT-dependent reperfusion injury to hepatocytes. Cultured rat hepatocytes were ...

Etoposide (VP-16) is known to promote cell apoptosis either in cancer or in normal cells as a side effect. This fact is preceded by the induction of several mitochondrial events, including increase in Bax/Bcl-2 ratio followed by cytochrome c release and consequent activation of caspase-9 and -3, reduction of ATP levels, depolarization of membrane potential (DeltaPsi) and rupture of the outer me...

Whereas alpidem is hepatotoxic, zolpidem is not. Despite closely related chemical structures, alpidem, but not zolpidem, is a peripheral benzodiazepine receptor (PBR) ligand, and is also more lipophilic than zolpidem. We compared their effects in isolated rat liver mitochondria and rat hepatocytes. Zolpidem did not affect calcium-induced mitochondrial permeability transition (MPT) in mitochondr...

weaken the binding of the protein to its targeted DNA but retain a similar protein structure. It is this second class that both gives rise to the adverse prognosis of DLBCL and often demonstrates allele-specific “gain-of-function mutations”5,6 that confers new properties on a mutant p53 protein. These mutant proteins apparently bind to other transcription factors (like p73) and alter their func...

Opening of a high-conductance pore conducting solutes of molecular mass <1,500 Da causes onset of the mitochondrial permeability transition (MPT). Cyclosporin A blocks this pore and prevents acute necrotic cell death in several models. Confocal microscopy directly visualizes onset of the MPT during acute cytotoxicity from the movement of the green-fluorescing fluorophore, calcein, into the mito...

BACKGROUND Mud pack therapy (MPT) influences the serum levels of several cytokines involved in chondrocyte metabolism and in the pathogenesis of osteoarthrosis. In fact, we have observed decreases of IL-1 and TNF-alpha, involved in cartilage inflammation and destruction, and increases of IGF-1 that have a protective influence on the cartilage. It is known that in osteoarthrosis MPT is also able...

Ischemic preconditioning (IPC) inhibits Ca(2+)-loading during ischemia which contributes to cardioprotection by inhibiting mechanical injury due to hypercontracture and biochemical injury through mitochondrial permeability transition (MPT) pores during reperfusion. However, whether remote-IPC reduced Ca(2+)-loading during ischemia and its subsequent involvement in inhibiting MPT pore formation ...