Biochemical and biophysical research communications
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Biochem. Biophys. Res. Commun. · Oct 2002
Functional CLOCK is not involved in the entrainment of peripheral clocks to the restricted feeding: entrainable expression of mPer2 and BMAL1 mRNAs in the heart of Clock mutant mice on Jcl:ICR background.
The mammalian circadian timing system consists of a central pacemaker in brain hypothalamus and damping oscillators in most peripheral tissues. To investigate the mechanism that controls circadian rhythms in the mammalian peripheral tissues, we examined the expression rhythm of mPer2, BMAL1, albumin D-site binding protein (DBP), and Rev-erbalpha mRNAs in the heart of homozygous Clock mutant mice on Jcl:ICR background under the temporal feeding restriction. Unexpectedly, the restricted feeding (RF) shifted the circadian phase of both mPer2 and BMAL1 mRNA expressions in the heart not only of wild-type mice but also of Clock mutant mice. ⋯ On the other hand, the expression levels of DBP and Rev-erbalpha mRNAs were blunted in Clock mutant mice not only under ad libitum but also under RF conditions. Thus, it seems that the rhythmic expression of Rev-erbalpha is not involved in the RF-induced circadian expression of BMAL1 mRNA, although REV-ERBalpha has been identified as a major regulator of BMAL1 transcription. Thus, the entraining mechanism of peripheral tissues to the RF seems to be different from that to the central clock in the suprachiasmatic nucleus.
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Biochem. Biophys. Res. Commun. · Sep 2002
Effect of Mg(2+) on the kinetics of guanine nucleotide binding and hydrolysis by Cdc42.
The biological activities of Rho family GTPases are controlled by their guanine nucleotide binding states in cell. Mg(2+) ions play key roles in guanine nucleotide binding and in preserving the structural integrity of GTPases. ⋯ In contrast to the cases of Ras and Rab proteins, which require Mg(2+) for the nucleotide binding and intrinsic hydrolysis of GTP, our results show that in the absence of Mg(2+), the binding affinity of GTP to Cdc42 is in the submicromolar concentration, and the Mg(2+) cofactor has only a minor effect on the Cdc42-catalyzed intrinsic hydrolysis rate of GTP. These results suggest that the intrinsic GTPase reaction mechanism of Cdc42 may differ significantly from that of other subfamily members of the Ras superfamily.
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Biochem. Biophys. Res. Commun. · Jun 2002
Role of CXC chemokines in the enhancement of LPS-induced neutrophil accumulation in the lung of mice by dexamethasone.
Lipopolysaccharide (LPS)-induced multiple organ injury was mediated in part by a transcription factor, nuclear factor-kappaB (NF-kappaB). Mice were pretreated with dexamethasone (DEX), an inhibitor of NF-kappaB activation, to elucidate its effects on LPS-induced early responses in vivo. ⋯ The suppression of plasma TNF-alpha levels by pretreatment with an anti-TNF-alpha antibody did not enhance LPS-induced neutrophil accumulation in the lung. These results demonstrate that the enhancement of LPS-induced neutrophil accumulation by DEX might be mediated by MIP-2 and not by TNF-alpha.
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Biochem. Biophys. Res. Commun. · Feb 2002
Orexins activate histaminergic neurons via the orexin 2 receptor.
Orexins (orexin A and B) are recently identified neuropeptides implicated in the regulation of vigilance states and energy homeostasis. We have shown here the physiological significance of histaminergic neurons in the orexin-induced arousal responses. Immunohistochemical and electron microscopic techniques revealed direct synaptic interaction between orexin-immunoreactive nerve terminals and histidine decarboxylase-immunoreactive neurons in the TMN. ⋯ Simultaneously recordings of electroencephalograph and electromyograph showed that intracerebroventricular infusion of orexin A significantly increased the awake state in the light phase. Central application of pyrilamine significantly inhibited this response. These results strongly suggest that activation of histaminergic neurons by orexins might be important for modulation of the arousal.
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Biochem. Biophys. Res. Commun. · Nov 2001
Involvement of the retinoblastoma (pRb)-E2F/DP pathway during antiproliferative effects of resveratrol in human epidermoid carcinoma (A431) cells.
Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic phytoalexin found in grapes, nuts, many other fruits, and red wine, is a potent antioxidant with anti-inflammatory and cancer-preventive properties. The mechanism(s) by which resveratrol imparts cancer chemopreventive effects has not been clearly defined. Earlier, we have shown that resveratrol treatment results in an induction of the cyclin kinase inhibitor WAF1/CIP1/p21 which, by inhibiting cyclin (E, D1, and D2) and cyclin-dependent kinases (cdk2, cdk4, and cdk6), results in a G0/G1-phase arrest followed by apoptosis of A431 human epidermoid carcinoma cells (Ahmad et al., Clin. ⋯ This suggests that resveratrol causes a downregulation of hyperphosphorylated pRb protein with a relative increase in hypophosphorylated pRb that, in turn, compromises with the availability of free E2F. We suggest that this series of events results in a stoppage of the cell cycle progression at the G1-->S phase transition thereby leading to a G0/G1 arrest and subsequent apoptotic cell death. To our knowledge, this is the first study showing the involvement of the pRb-E2F/DP pathway as a mechanism of the cancer-chemopreventive effects of resveratrol.