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1.
Seung Hyeok Seok Jong-Ik Heo Ji-Hye Hwang Yi-Rang Na Jang-Hyuk Yun Eun Hui Lee Jong-Wan Park Chung-Hyun Cho 《Molecules and cells》2013,35(6):550-556
The angiopoietin/Tie2 system is an important regulator of angiogenesis and inflammation. In addition to its functions in endothelial cells, Tie2 expression on non-endothelial cells allows for angiopoietin ligands to stimulate the cells. Although Ang1 is a strong Tie2 receptor agonist, little is known regarding the effect of Ang1 on non-endothelial cells, such as monocytes and macrophages. In this study, we found that Ang1 functionally binds to and stimulates monocytes via p38 and Erk1/2 phosphorylation. Ang1-mediated monocyte stimulation is associated with proinflammatory cytokine TNF-α expression. We also determined that Ang1 switched macrophage differentiation toward a pro-inflammatory phenotype, even in the presence of an anti-inflammatory mediator. These findings suggest that Ang1 plays a role in stimulating pro-inflammatory responses and could provide a new strategy by which to manage inflammatory responses. 相似文献
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Role of apoptosis-inducing factor in myocardial cell death by ischemia-reperfusion 总被引:14,自引:0,他引:14
Kim GT Chun YS Park JW Kim MS 《Biochemical and biophysical research communications》2003,309(3):619-624
Although apoptosis contributes to myocardial cell death in the ischemia-reperfused heart, the molecular basis of apoptosis is poorly understood. Apoptosis-inducing factor (AIF) has been characterized as a caspase-independent death effector. Upon the induction of apoptosis, mitochondrial AIF is released to the cytoplasm and then enters the nucleus, in which it induces chromatin condensation and 50 kbp DNA fragmentation. In the present study, we examined the role of AIF in ischemia-reperfusion injury in isolated rat hearts. AIF was detected in the cytosolic and nuclear fractions of hearts subjected to ischemia-reperfusion, whereas it was detected only in the mitochondria of control hearts. Moreover, AIF release increased in a reperfusion time-dependent manner. Pulse field gel electrophoresis revealed that 50 kbp DNA fragments were produced by ischemia/reperfusion. In contrast, cytochrome c release and the activation of caspase-3 did not occur to a significant extent. Moreover, ischemic preconditioning attenuated the AIF release and the 50 kbp DNA fragmentation. These results suggest that AIF-dependent apoptosis is likely to attribute to myocardial cell death in the ischemia-reperfused heart and that it is related with the protective effect of ischemic preconditioning. 相似文献
3.
Hyun-Woo Shin Chung-Hyun Cho Jong-Wan Park 《Biochemical and biophysical research communications》2010,398(2):205-771
Sunitinib (SU11248, Sutent®) is a class III/V receptor tyrosine kinase (RTK) inhibitor that exhibits potent anti-angiogenic and anticancer activities. Preclinical studies demonstrated that the sunitinib effects are attributed to inhibition of VEGFR and PDGFR phosphorylation. However, even in colon cancer cells lacking sunitinib-targeted RTKs, sunitinib effectively inhibits tumor growth in a xenograft model, and this raises a question about the mechanism underlying the in vivo anticancer action of sunitinib. Since hypoxia is a critical microenvironment that tumors face, we addressed the possibility that sunitinib deregulates tumor adaptation to hypoxia. First we found that sunitinib limits the colony growth of HT-29, which is a colon adenocarcinoma cell line lacking the RTKs, and that HIF-1α in the colonies is decreased by sunitinib. In cultured HT-29 cells, sunitinib suppressed HIF-1α under hypoxic conditions. Moreover, sunitinib repressed the activity of HIF-1α and subsequently decreased the expressions of HIF-1 downstream genes. Mechanistically, sunitinib blocked the 5′-UTR-dependent translation of HIF-1α. The HIF-1α suppression by sunitinib was also reproduced in a VHL-null renal cell carcinoma cell line, where HIF-1α is not degradable. In conclusion, the sunitinib inhibition of HIF-1 signaling could restrain tumor progression in hypoxic regions, which may contribute to anticancer effect of sunitinib. 相似文献
4.
An H Kim NJ Jung JW Jang H Park JW Suh YG 《Bioorganic & medicinal chemistry letters》2011,21(21):6297-6300
Design, synthesis and insight into the structure-activity relationship (SAR) of 1,3-disubstituted indazoles as novel HIF-1 inhibitors are described. In particular, the substituted furan moiety on indazole skeleton as well as its substitution pattern turns out crucial for the high HIF-1 inhibition. 相似文献
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Cho KJ Shim JH Cho MC Choe YK Hong JT Moon DC Kim JW Yoon DY 《Journal of cellular biochemistry》2005,96(4):869-878
Melanocortins, besides their central roles, have also recently been reported to regulate adipocyte metabolism. In this study, we attempted to characterize the mechanism underlying alpha-melanocyte-stimulating hormone (MSH)-induced lipolysis, and compared it with that of the adrenocorticotrophin hormone (ACTH) in 3T3-L1 adipocytes. Similar to ACTH, MSH treatment resulted in the release of glycerol into the cell supernatant. The activity of hormone-sensitive lipase, a rate-limiting enzyme, which is involved in lipolysis, was significantly increased by MSH treatment. In addition, a variety of kinases, including protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) were also phosphorylated as the result of MSH treatment, and their specific inhibitors caused a reduction in MSH-induced glycerol release and HSL activity, indicating that MSH-induced lipolysis was mediated by these kinases. These results suggest that PKA and ERK constitute the principal signaling pathways implicated in the MSH-induced lipolytic process via the regulation of HSL in 3T3-L1 adipocytes. 相似文献
7.
Jong-Wan Lee Nam-Hong Kim Eun-Ji Kim Hun Heo Young Jun Jung Jung Ro Lee Yung-Hoon Park Seong-Cheol Park Mi-Kyeong Jang 《Biotechnology and Bioprocess Engineering》2016,21(4):508-514
Norfloxacin is a broad-spectrum synthetic antibacterial agent that has been used to treat complicated urinary tract infections. However, the poor water-solubility of norfloxacin limits its bioavailability. The aim of the present study was to synthesize water-soluble norfloxacin derivate through adding isosorbide via enzymatic catalyst (Green chemistry) and to evaluate its physiological and biological properties. Isosorbide-dinorfloxacin (ISDNf) was synthesized by enzymatic esterification between the carboxyl group of norfloxacin and two hydroxyl groups of isosorbide. Chemical structure and water-solubility of ISDNf purified by HPLC was investigated by using 1H NMR and MALDITOF, and optical spectrometry, respectively. Antibacterial effects of ISDNf were evaluated against 7 drug-susceptible and 7 drug-resistant bacteria. ISDNf, which was successfully synthesized, was water-soluble at 10,000 mg/L, compared that free norfloxacin was water-insoluble at 100 mg/L. The antibacterial efficiency of ISDNf was maintained in drugsusceptible bacteria, while that was enhanced in drugresistant bacteria. Additionally, its cytotoxicity in mammalian cells was remarkably reduced and its solid diffusion capacity was increased. The increased water-solubility, antibacterial efficacy, and diffusion capacity and reduced cytotoxicity of ISDNf suggests that it could potentially be developed as a novel prodrug. 相似文献
8.
Expression of CD95 and CD95L on astrocytes in the CA1 area of the immature rat hippocampus after hypoxia-ischemia injury 总被引:1,自引:0,他引:1
Kim MJ Lim HS Yoo YB Lee YI Hahm DH Lee HJ Jung KW Kim JW Yoe SM Chung DC Chang YP 《Comparative medicine》2007,57(6):581-589
The immature brain is affected profoundly by hypoxia-ischemia (HI) injury, which can lead to permanent neurologic sequelae in survivors. Neuronal degeneration after HI injury usually is achieved through apoptosis. Both CD95 and its natural ligand, CD95L, which are key molecules in the regulation of apoptosis, are constitutively expressed by neurons and astrocytes during embryonic and early postnatal stages. Further, CD95 or CD95L may have a functional relationship in glial cells and lead to apoptosis of these cells. The hippocampus, especially the CA1 area, is particularly susceptible to HI injury. We therefore investigated the temporal and spatial alterations in CD95 and CD95L expression in the CA1 area of 7-d-old rats after unilateral ligation of the carotid artery. Using immunohistochemistry and Western blotting, we showed that expression of CD95 and CD95L in the hippocampus peaked at 12 h and then decreased. In addition, we used terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end-labeling to demonstrate apoptosis among CD95- and CD95L-reactive cells. Our findings show that increases in the expression of CD95 and CD95L after HI injury may involve astrocytic apoptosis in the 7-d-old rat hippocampus, and these molecules may act as targets or inducers of cell death. 相似文献
9.
Ji-Seon Kim Sung Joon Kim Jong-Wan Park Kyong Soo Park Yang-Sook Chun 《Biochemical and biophysical research communications》2009,379(4):1048-1053
Aryl hydrocarbon receptor nuclear translocator (ARNT) has been known to participate in cellular responses to xenobiotic and hypoxic stresses, as a common partner of aryl hydrocarbon receptor and hypoxia inducible factor-1/2α. Recently, it was reported that ARNT is essential for adequate insulin secretion in response to glucose input and that its expression is downregulated in the pancreatic islets of diabetic patients. In the present study, the authors addressed the mechanism by which ARNT regulates insulin secretion in the INS-1 insulinoma cell line. In ARNT knock-down cells, basal insulin release was elevated, but insulin secretion was not further stimulated by a high-glucose challenge. Electrophysiological analyses revealed that glucose-dependent membrane depolarization was impaired in these cells. Furthermore, KATP channel activity and expression were reduced. Of two KATP channel subunits, Kir6.2 was found to be positively regulated by ARNT at the mRNA and protein levels. Based on these results, the authors suggest that ARNT expresses KATP channel and by so doing regulates glucose-dependent insulin secretion. 相似文献
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