Journal of neurochemistry
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Journal of neurochemistry · Jun 2007
Regulation of neuronal nitric oxide synthase exon 1f gene expression by nuclear factor-kappaB acetylation in human neuroblastoma cells.
The neuronal nitric oxide synthase (nNOS) is predominantly expressed in nervous tissues and subject to complex transcriptional controls. To determine the effect of acetylation on nNOS expression, human neuroblastoma SK-N-SH cells were treated with trichostatin A (TSA), a histone deacetylase inhibitor. As a consequence, total and exon 1f-specific nNOS mRNA, nNOS protein and nNOS-derived nitric oxide production were increased. ⋯ Luciferase assays revealed that TSA up-regulated the transcriptional activity of the nNOS 1f promoter through NF-kappaB-mediated transactivation. Taken together, we demonstrate that acetylation plays a crucial role in nNOS expression and suggest that acetylation of NF-kappaB p65 and p50 subunits by TSA treatment may augment their DNA-binding affinities, thereby activating the nNOS exon 1f promoter. It may be one of the mechanisms by which acetylation modulates nNOS expression and nitric oxide output in SK-N-SH cells and may be the molecular basis for certain neurological disorders.
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Journal of neurochemistry · Jun 2007
Mitochondrial dysfunction early after traumatic brain injury in immature rats.
Mitochondria play central roles in acute brain injury; however, little is known about mitochondrial function following traumatic brain injury (TBI) to the immature brain. We hypothesized that TBI would cause mitochondrial dysfunction early (<4 h) after injury. Immature rats underwent controlled cortical impact (CCI) or sham injury to the left cortex, and mitochondria were isolated from both hemispheres at 1 and 4 h after TBI. ⋯ Four hours after TBI, pyruvate dehydrogenase complex activity and cytochrome c content (ipsilateral/contralateral ratios) were lower in TBI mitochondria. These data demonstrate abnormal mitochondrial function early (