Biological signals最新文献

In neonatal rat gonadotrophs, melatonin acts through the high-affinity membrane-bound receptors to inhibit GnRH-induced [Ca2+]i increase. GnRH increases [Ca2+]i primarily by mobilization from the inositol trisphosphate-sensitive pool followed by Ca2+ influx through the voltage-sensitive channels. Melatonin inhibits the GnRH-induced [Ca2+]i increase. When added after the GnRH-induced spike, melatonin decreases [Ca2+]i in 52% of the gonadotrophs. The effect of melatonin is dependent on extracellular Ca2+ and may be mimicked by Ca2+-free medium or verapamil. When added before GnRH, melatonin inhibits the [Ca2+]i spike. This effect of melatonin is independent of extracellular Ca2+ as it persists in Ca2+-free medium. These findings indicate that melatonin blocks Ca2+ mobilization as well as Ca2+ influx in the gonadotrophs.

The ability of melatonin to protect iron-induced lipid peroxidation was studied in various rat cell membranes. The concentration of cellular membrane malondialdehyde (MDA) was used as an index of induced oxidative membrane damage. Cell membranes from the brain, heart, kidney and liver of the male Sprague-Dawley rat were incubated with ferric ammonium citrate (20 microg/ml iron) alone for 3 h and concomitant with varying concentrations of melatonin ranging from 125 to 2,000 microM. The basal MDA levels of all the cell membranes were 25.0+/-1.4 (brain), 21.2+/-0.2 (heart), 10.0+/-0.9 (kidney) and 20.7+/-0.4 (liver) microM/g membrane protein, and the highest lipid peroxidation after exposure to iron occurred in the kidney (314.4%), followed by the heart (151.3%), the liver (130.4%) and the brain (121.7%). This peroxidative effect was completely (ED50 846.7 microM for the heart) and partially suppressed by melatonin (ED50 462.1 microM for the brain, 178.3 microM for the kidney and 886.6 microM for the liver). This inhibition effect on MDA production by these cell membranes was also found - except for the liver - if melatonin was used alone. These results show that the direct effect of lipid peroxidation on cellular membrane following iron exposure is markedly reduced by melatonin.

Recent progress in research on retinal circadian rhythmicity is reviewed. Important advances include the discovery that circadian oscillators are present in the retinas of diverse vertebrate species, and evidence that circadian rhythmicity is generated by the photoreceptor cells. Research on the cellular and molecular mechanisms of photoreceptor circadian rhythms has revealed that expression of a subset of genes associated with photoreception, melatonin synthesis and transcriptional control are regulated by a circadian oscillator. Finally, it has been found that cAMP mimics darkness in resetting the phase of the retinal photoreceptor circadian oscillator, suggesting that it may be a component of a transduction pathway for entrainment of the oscillator.

Intronless mRNAs were classified into two classes based on the sensitivities of their expression to the inhibitory effect of TAgRex, a dominant-negative mutant of the Rex protein of human T cell leukemia virus type I, and their abilities to express the genes encoded in the intron of the human immunodeficiency virus (HIV) genome. Interferon-alpha mRNA could not induce the expression of the env gene of HIV, and its expression was resistant to TAgRex. In contrast, the posttranscriptional regulatory element (PRE), necessary for the nucleo-cytoplasmic export of mRNAs of hepatitis B virus, induced expression of the chloramphenicol acetyl transferase gene located within the intron of the HIV genome. PRE-mediated expression was inhibited by TAgRex. Thus, these results suggest that there are at least two distinct pathways for intronless mRNA expression, one related to and the other unrelated to Rev and Rex functions.