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971.
972.
Role of Galpha12 and Galpha13 as novel switches for the activity of Nrf2, a key antioxidative transcription factor 总被引:1,自引:0,他引:1 下载免费PDF全文
Cho MK Kim WD Ki SH Hwang JI Choi S Lee CH Kim SG 《Molecular and cellular biology》2007,27(17):6195-6208
Galpha12 and Galpha13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress. This study investigated the regulation of Nrf2 by Galpha12 and Galpha13. A deficiency of Galpha12, but not of Galpha13, enhanced Nrf2 activity and target gene transactivation in embryo fibroblasts. In mice, Galpha12 knockout activated Nrf2 and thereby facilitated heme catabolism to bilirubin and its glucuronosyl conjugations. An oligonucleotide microarray demonstrated the transactivation of Nrf2 target genes by Galpha12 gene knockout. Galpha12 deficiency reduced Jun N-terminal protein kinase (JNK)-dependent Nrf2 ubiquitination required for proteasomal degradation, and so did Galpha13 deficiency. The absence of Galpha12, but not of Galpha13, increased protein kinase C delta (PKC delta) activation and the PKC delta-mediated serine phosphorylation of Nrf2. Galpha13 gene knockout or knockdown abrogated the Nrf2 phosphorylation induced by Galpha12 deficiency, suggesting that relief from Galpha12 repression leads to the Galpha13-mediated activation of Nrf2. Constitutive activation of Galpha13 promoted Nrf2 activity and target gene induction via Rho-mediated PKC delta activation, corroborating positive regulation by Galpha13. In summary, Galpha12 and Galpha13 transmit a JNK-dependent signal for Nrf2 ubiquitination, whereas Galpha13 regulates Rho-PKC delta-mediated Nrf2 phosphorylation, which is negatively balanced by Galpha12. 相似文献
973.
974.
Choi IY Kim SJ Jeong HJ Park SH Song YS Lee JH Kang TH Park JH Hwang GS Lee EJ Hong SH Kim HM Um JY 《Molecular and cellular biochemistry》2007,305(1-2):153-161
The citrus unshiu peel has been used traditionally as a medicine to improve bronchial and asthmatic conditions or cardiac
and blood circulation in Korea, China, and Japan. Here, we report the effects of citrus unshiu peel water extract (CPWE) on
the phorbol myristate acetate (PMA) + calcium ionophore A23187-induced hypoxia-inducible factor-1α (HIF-1α) activation and
inflammatory cytokine production from the human mast cell line, HMC-1 cells. We compared CPWE with hesperidin, a common constituent
of citrus unshiu. CPWE and hesperidin inhibited the PMA + A23187-induced HIF-1α expression and the subsequent production of
vascular endothelial growth factor (VEGF). In addition, CPWE suppressed PMA + A23187-induced phosphorylation of the extracellular
signal-regulated kinase (ERK). We also show that the increased cytokines interleukin (IL)-1β, IL-8, and tumor necrosis factor
(TNF)-α level was significantly inhibited by treatment of CPWE or hesperidin. In the present study, we report that CPWE and
hesperidin are inhibitors of HIF-1α and cytokines on the mast cell-mediated inflammatory responses. 相似文献
975.
976.
Park K Lee S Kang SJ Choi S Shin KS 《Biochemical and biophysical research communications》2007,361(3):718-724
Anxiety is thought to be influenced by neuronal excitability in basolateral nucleus of the amygdala (BLA). However, molecules that are critical for regulating excitability of BLA neurons are yet to be determined. In the present study, we have examined whether hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels, which mediate the depolarizing cation current, can control the neuronal excitability. HCN channel-like activity appeared to be detected in BLA principal neurons. ZD7288, a specific blocker for HCN channels, increased the input resistance of membrane, hyperpolarized resting membrane potential, and enhanced action potential firing in BLA principal neurons. The blockade of HCN channels facilitated temporal summation of repetitively evoked excitatory postsynaptic potentials, suggesting that suppression of HCN channel activity in principal neurons can accelerate the propagation of synaptic responses onto the axon hillock. Thus, our findings have laid foundation for studies to reveal how HCN channel activity in BLA principal neurons regulates anxiety in vivo. 相似文献
977.
Moon HS Lee HG Seo JH Chung CS Guo DD Kim TG Choi YJ Cho CS 《Biochemical and biophysical research communications》2007,356(4):955-960
It has long been recognized that leptin, a hormone made by adipocytes, is an important circulating signal for the regulation of body weight. In addition, matrix metalloproteinase (MMP), especially MMP-2, an adipocyte-secreted protein which promotes multi-cellular adipose clusters, is up-regulated in obesity. The present study is designed to evaluate whether trans-10,cis-12 conjugated linoleic acid (t-CLA) can suppress leptin-induced MMP-2 secretion in 3T3-L1 cells. The result showed that expressions of adipocyte marker proteins were significantly reduced by t-CLA-treated cultures, but not by linoleic acid (LA)-treated ones. Interestingly, MMP-2 secretion was significantly increased by leptin-treated cultures, thereby leading to accelerate adipocyte differentiation, indicating that MMP-2 was a necessary mediator of adipogenesis. However, increasing concentration of t-CLA significantly reduced leptin-induced MMP-2 secretion and triglyceride (TG) content. These findings provide support for a role for t-CLA in the regulation of metabolism in leptin-induced adipose tissue development. 相似文献
978.
Hatanaka H Takada S Choi YL Fujiwara S Soda M Enomoto M Kurashina K Watanabe H Yamashita Y Sugano K Mano H 《Biochemical and biophysical research communications》2007,356(3):723-726
Colorectal cancer (CRC) is one of the leading causes of cancer death in humans. In order to identify novel cancer-promoting genes in CRC, we here constructed a retroviral cDNA expression library from a CRC cell line RKO, and used it for a focus formation assay with mouse 3T3 fibroblasts, leading to the identification of 42 independent cDNAs. One of such cDNAs turned out to encode purinergic receptor P2Y, G-protein coupled, 2 (P2RY2). The oncogenic potential of P2RY2 was confirmed in vitro with the focus formation assay as well as soft agar-growth assay, and also in vivo with a tumorigenicity assay in nude mice. While our P2RY2 cDNA encodes a protein with two amino-acid substitutions compared to the reported one, we have confirmed that the wild-type P2RY2 has a strong transforming potential as well. These results indicate an unexpected role of P2RY2 in the carcinogenesis of human cancers. 相似文献
979.
980.
Park CH Lee J Jung HY Kim MJ Lim SH Yeo HT Choi EC Yoon EJ Kim KW Cha JH Kim SH Chang DJ Kwon DY Li F Suh YG 《Bioorganic & medicinal chemistry》2007,15(20):6517-6526
The quinolone analog SQ-4004 has been identified as a potentially excellent anti-ischemic agent, which exhibited highly potent efficacy in reducing infarct volume size in vivo rat MCAO model (32.1% at 0.01mg/kg) and potent cardioprotective effect at myocardial infarction in vivo model (26.6% at 0.01mg/kg) while it exhibited highly reduced anti-bacterial activity. The mechanistic study revealed that the anti-ischemic activity might exert via an anti-apoptotic pathway, which implies its therapeutic uses against the ischemic cell injuries including ischemic stroke and ischemic heart disease. 相似文献