Biochemical and biophysical research communications
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Biochem. Biophys. Res. Commun. · Oct 2003
ReviewNew patterns of inheritance in mitochondrial disease.
With the identification of a patient with mutated mitochondrial DNA (mtDNA) of paternal origin, it has been unequivocally proven that not only does paternal mtDNA survive in the zygote, but it can also contribute substantially to the mtDNA pool of adult, human skeletal muscle. The questions are: how often does paternal mtDNA inheritance occur and what mechanisms are involved? In this paper, we will review current knowledge on the fate of sperm mitochondria after fertilization and discuss the impact paternal inheritance may have on our understanding of mitochondrial biology.
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Biochem. Biophys. Res. Commun. · Oct 2003
Biphasic action of midazolam on GABAA receptor-mediated responses in rat sacral dorsal commissural neurons.
The effect of the benzodiazepine agonist midazolam on gamma-aminobutyric acid(A) (GABA(A)) receptor-mediated currents was investigated in neurons acutely dissociated from the rat sacral dorsal commissural nucleus (SDCN) using the nystatin-perforated patch-recording configuration under voltage-clamp conditions. Midazolam displayed a biphasic effect on GABA responses. Low concentrations of midazolam (1nM-10 microM) reversibly potentiated GABA (3 microM)-activated Cl(-) currents (I(GABA)) in a bell-shaped manner, with the maximal facilitary effect at 0.1 microM; whereas at higher concentrations (above 10 microM), midazolam had an antagonistic effect on I(GABA). ⋯ The benzodiazepine receptor antagonist, flumazenil, abolished the facilitary effect of low concentrations of midazolam rather than the antagonism of I(GABA) induced by high doses of midazolam. In addition, activation of protein kinase C prevented the inhibitory effect of midazolam at higher concentrations, but did not influence the effect of midazolam at low concentrations. These results indicate that midazolam interacts with another distinct site other than the central benzodiazepine receptors on GABA(A) receptors as an antagonist at higher concentrations in SDCN neurons.
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Biochem. Biophys. Res. Commun. · Sep 2003
Effects of c-fos antisense oligodeoxynucleotide on 5-HT-induced upregulation of preprodynorphin, preproenkephalin, and glutamic acid decarboxylase mRNA expression in cultured rat spinal dorsal horn neurons.
Effects of c-fos antisense oligodeoxynucleotide (ASO) on serotonin (5-HT)-induced upregulation of preprodynorphin (ppDyn), preproenkephalin (ppEnk), and glutamic acid decarboxylase (GAD), a special chemical marker for gamma-aminobutyric acid (GABA) neurons, mRNAs in cultured spinal dorsal horn neurons were investigated in order to extend our understanding of expressions of opioid peptides and GABA in spinal cord regulated by the descending serotonergic efferents. Reverse transcription-polymerase chain reaction analysis revealed a time-course increase in the expression of mRNAs encoding c-fos, ppDyn, ppEnk, and GAD after administration of 5-HT (100 nM). Administration of c-fos ASO (0.02 nM) 30 min prior to 5-HT application markedly blocked the expression of c-fos gene. ⋯ These results suggest that the serotoningic raphe-spinal efferents might play an important role in regulating the synthesis of enkephalin, dynorphin, and GABA in the spinal dorsal horn neurons. The immediate early oncogene c-fos might be involved in the 5-HT-induced increase in ppDyn and ppEnk expression. However, under the present experimental conditions, c-fos does not seem to be associated with the upregulation of GAD mRNA induced by 5-HT.
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Biochem. Biophys. Res. Commun. · Feb 2003
Identification and characterization of two new human mu opioid receptor splice variants, hMOR-1O and hMOR-1X.
The mouse gene encoding the mu opioid receptor, Oprm, undergoes extensive alternatively splicing, with 14 variants having been identified. However, only one variant of human mu opioid receptor gene (Oprm), MOR-1A, has been described. We now report two novel splice variants of the human Oprm gene, hMOR-1O and hMOR-1X. ⋯ Northern blots revealed several bands with the exon O probe in both human neuroblastoma BE(2)C cells and human brain and a single band (5.5kb) with the exon X probe in selected human brain regions. When transfected into CHO cells, both variants showed high selectivity for mu opioids in binding assays. These two new human mu opioid receptors are the first human MOR-1 variants containing new exons and suggest that the complex splicing present in mice may extend to humans.
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Biochem. Biophys. Res. Commun. · Dec 2002
alpha- and beta-secretase: profound changes in Alzheimer's disease.
The amyloid plaque, a neuropathological hallmark of Alzheimer's disease, is produced by the deposition of beta-amyloid (Abeta) peptide, which is cleaved from Amyloid Precursor Protein (APP) by the enzyme beta-secretase. Only small amounts of Abeta form in normal brain; more typically this is precluded by the processing of APP by alpha-secretase. ⋯ Since alpha-secretase is present principally in neurons known to be vulnerable in Alzheimer's disease, and there is known competition between alpha- and beta-secretase for the substrate APP, it is significant that the majority of Alzheimer samples tested here were low in alpha-secretase. Eighty percent of Alzheimer brains examined had an increase in beta-secretase, a decrease in alpha-secretase, or both; which may account for the means by which the majority of people develop Alzheimer's disease.