Abstract:
:Melatonin is neuroprotective because of its antioxidative action, but it also can modify neuronal vulnerability by altering gene expression. 5-Lipoxygenase (5-LO) gene expression is suppressed by the binding of melatonin to its high-affinity nuclear receptors. Recently, we reported that in rats the melatonin deficiency elicited by pinealectomy increases hippocampal susceptibility to excitotoxic injury. Here we have hypothesized that pinealectomy may increase hippocampal vulnerability by eliminating the tonic inhibitory action of melatonin on 5-LO gene expression. Sham-pinealectomized controls and pinealectomized rats were killed 15 days after surgery. Their hippocampi were dissected, and total RNA was extracted and processed for quantitative reverse transcription-polymerase chain reaction assay of 5-LO and cyclophilin mRNAs. Mutated primers were used as internal standards to assay attomole quantities of these two specific mRNAs per microgram of total RNA; the ratio 5-LO/cycophilin was used to compare samples from control and pinealectomized rats. Pinealectomy increased hippocampal 5-LO mRNA content by about threefold. These results support our hypothesis that melatonin deficiency may abate the tonic inhibition of 5-LO mRNA expression and thereby up-regulate 5-LO gene expression, which in turn would increase the brain's synthesis rate of potentially harmful eicosanoids, leukotrienes.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Uz T,Longone P,Manev Hdoi
10.1046/j.1471-4159.1997.69052220.xsubject
Has Abstractpub_date
1997-11-01 00:00:00pages
2220-3issue
5eissn
0022-3042issn
1471-4159journal_volume
69pub_type
杂志文章abstract::Genomic and cDNA clones encoding the rat D1 receptor were isolated and sequenced. Comparison of the D1 receptor cDNA and genomic sequences revealed that the rat D1 receptor gene is organized into two exons separated by a small intron in the 5' untranslated region of its mRNA. The transcription start site is located 86...
journal_title:Journal of neurochemistry
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doi:10.1111/j.1471-4159.1992.tb11023.x
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pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb01873.x
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.64051928.x
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.67020473.x
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journal_title:Journal of neurochemistry
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pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1997-05-01 00:00:00
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