Medical Anatomy Commons^™

Vdac-Dependent Permeabilization Of The Outer Mitochondrial Membrane By Superoxide Induces Rapid And Massive Cytochrome C Release., M Madesh, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Enhanced formation of reactive oxygen species (ROS), superoxide (O2*-), and hydrogen peroxide (H2O2) may result in either apoptosis or other forms of cell death. Here, we studied the mechanisms underlying activation of the apoptotic machinery by ROS. Exposure of permeabilized HepG2 cells to O2*- elicited rapid and massive cytochrome c release (CCR), whereas H2O2 failed to induce any release. Both O2*- and H2O2 promoted activation of the mitochondrial permeability transition pore by Ca2+, but Ca2+-dependent pore opening was not required for O2*--induced CCR. Furthermore, O2*- alone evoked CCR without damage of the inner mitochondrial membrane barrier, as mitochondrial membrane potential …

Eliciting The Low-Activity Aldehyde Dehydrogenase Asian Phenotype By An Antisense Mechanism Results In An Aversion To Ethanol., E Garver, Tu Gc, Q N Cao, M Aini, F Zhou, Y Israel

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A mutation in the gene encoding for the liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes the activity of this enzyme and results in elevations in blood acetaldehyde upon ethanol consumption, a phenotype that greatly protects against alcohol abuse and alcoholism. We have determined whether the administration of antisense phosphorothioate oligonucleotides (ASOs) can mimic the low-activity ALDH2-2 Asian phenotype. Rat hepatoma cells incubated for 24 h with an antisense oligonucleotide (ASO-9) showed reductions in ALDH2 mRNA levels of 85% and ALDH2 (half-life of 22 h) activity of 55% equivalent to a >90% inhibition in ALDH2 …

Acidification-Induced Sensitization To Thermoradiotherapy In Breast Cancer, Dennis B. Leeper, L T. Komarnicky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Hyperthermia is an extensively studied cytotoxic agent, with strong radio- and chemosensitizing potential. Recent positive clinical trials combining superficial or deep heating techniques with radiation therapy strongly support a role for hyperthermia as an adjuvant to radiation. Many in vitro and in vivo studies have shown that acute extracellular acidification will compromise fundamental protective cellular responses and enhance tumor response to hyperthermia and chemotherapy.

Breast cancers, like most other tumors, exhibit elevated levels of lactate production that provides a basis for selective acidification. A phase I/II clinical trial is underway to test the hypothesis that hyperglycemia-induced acute acidification will sensitize …

Methods For Volume Measurement In 3d Images, Kevin J. Black

Kevin J. Black, MD