BDNF transgene improves ataxic and motor behaviors in stargazer mice.

The stargazer (stg) mouse exhibits severe cerebellar ataxia, abnormal motor behavior, and absence epilepsy. Selective failure of cerebellar brain-derived neurotrophic factor (BDNF) expression is one of the molecular defects in stg mutant. To determine the in vivo effect of BDNF replacement on cerebellar function, we generated a double mutant line of stg-BDNF mice by crossbreeding BDNF-overexpressing transgenics with stg mutants.

Tamoxifen induces oxidative stress and mitochondrial apoptosis via stimulating mitochondrial nitric oxide synthase.

Tamoxifen is an anticancer drug that induces oxidative stress and apoptosis via mitochondria-dependent and nitric oxide (NO)-dependent pathways. The present report shows that tamoxifen increases intramitochondrial ionized Ca(2+) concentration and stimulates mitochondrial NO synthase (mtNOS) activity in the mitochondria from rat liver and human breast cancer MCF-7 cells. By stimulating mtNOS, tamoxifen hampers mitochondrial respiration, releases cytochrome c, elevates mitochondrial lipid peroxidation, increases protein tyrosine nitration of certain mitochondrial proteins, decreases the catalytic activity of succinyl-CoA:3-oxoacid CoA-transferase, and induces aggregation of mitochondria.

Mitochondrial cytochrome c reacts with nitric oxide via S-nitrosation.

The present study demonstrates that mitochondrial cytochrome c reacts with the thiol-reacting agent N-ethylmaleimide (NEM) to produce a one NEM-adducted cytochrome c. Mitochondrial cytochrome c also reacts with 5,5'-dithio-bis-(2-nitrobenzoic acid) and 1-chloro-2,4-dinitrobenzene in a manner prevented with NEM or iodoacetic acid (IAA). NEM-treated cytochrome c has lower reducibility and lower function to support mitochondrial oxygen consumption.