Biomedical subjects

Taeg Kyu Kwon

Publications and source records attributed to Taeg Kyu Kwon.

At least 37 records · Page 2Linked to original sources

PubMed2005

Arsenic trioxide induces Hsp70 expression via reactive oxygen species and JNK pathway in MDA231 cells.

In the present study, we determined the molecular pathways that induce the heat shock proteins (Hsps) after treatment of cells with arsenic trioxide. Administration of arsenic trioxide to MDA231 cells leads to induce Hsp70, which is accompanied by generation of reactive oxygen species (ROS) and activation of c-Jun N-terminal kinase (JNK). We showed that arsenic trioxide-induced Hsp70 expression was caused by activation of ROS and prevented by the antioxidant N-Acetyl-Cysteine (NAC). SP600125 and dominant-negative SEK suppressed Hsp70 promoter-driven reporter gene expression, suggesting that JNK would be preferentially associated with the protective heat shock response against arsenic trioxide stress. In addition, SP600125, a specific JNK inhibitor, significantly reduced the amount of phosphorylated HSF1 upon administration of arsenic trioxide. It is likely that Hsp70 expression against arsenic trioxide exposure protects cells from oxidative injury and apoptotic cell death by means of JNK activity.

Acetylcysteine↗

PubMed2005

Activation of human cancer/testis antigen gene, XAGE-1, in tumor cells is correlated with CpG island hypomethylation.

Expression of the XAGE-1 antigen is restricted to germ cells of the testis and a variety of neoplastic tissues. To date, the molecular mechanism for regulating expression of this cancer/testis antigen gene has been unknown. To evaluate methylation as a potential mechanism for regulating expression of this gene, we first correlated gene methylation status (measured by sequencing of bisulfide-modified DNA and COBRA) to expression of XAGE-1 mRNA in normal and cancerous cells. This analysis revealed dense methylation of the CpG island in the XAGE-1 gene promoter for the normal and cancerous cells that do not express this gene but loss of this methylation in normal testis, cancer cell lines and the primary gastric cancers where the gene is highly expressed. Further supporting the role of methylation in regulating expression of XAGE-1 were observations that treatment of 2 heavily methylated cell lines, SNU620 and HT29, with 5'-aza-deoxycytidine resulted in demethylation of XAGE-1 promoter and corresponding expression of this gene. Finally, we cloned various segments of the CpG-rich XAGE-1 gene promoter linked to a luciferase reporter construct and transiently transfected this construct into HCT116 cells. These experiments confirmed transcriptional regulatory activity for the promoter region that incorporates the CpG island and demonstrated that in vitro methylation of this island results in loss of promoter activity. Collectively, these studies indicate that XAGE-1 expression in normal and cancerous tissues is regulated by methylation of the CpG island in the gene promoter.

Antigens, Neoplasm↗

PubMed2005

Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5).

Curcumin exhibits anti-inflammatory and antitumor activities. Although its functional mechanism has not been elucidated so far, numerous studies have shown that curcumin induces apoptosis in cancer cells. In the present study, we show that subtoxic concentrations of curcumin sensitize human renal cancer cells to the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. This apoptosis induced by the combination of curcumin and TRAIL is not interrupted by Bcl-2 overexpression. We found that treatment with curcumin significantly induces death receptor 5 (DR5) expression both at its mRNA and protein levels, accompanying the generation of the reactive oxygen species (ROS). Not only the pretreatment with N-acetylcystine but also the ectopic expression of peroxiredoxin II, an antioxidative protein, dramatically inhibited the apoptosis induced by curcumin and TRAIL in combination, blocking the curcumin-mediated DR5 upregulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by ROS-mediated DR5 upregulation.

Antineoplastic Agents↗

PubMed2005

Ascochlorin inhibits matrix metalloproteinase-9 expression by suppressing activator protein-1-mediated gene expression through the ERK1/2 signaling pathway: inhibitory effects of ascochlorin on the invasion of renal carcinoma cells.

The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. Here we examined the effect of ascochlorin, a prenyl-phenol anti-tumor compound from the fungus Ascochyta viciae, on the regulation of signaling pathways that control MMP-9 expression in human renal carcinoma (Caki-1) cells. Ascochlorin reduced the invasive activity of Caki-1 cells and inhibited phorbol 12-myristate 13-acetate-induced increases in MMP-9 expression and activity in a dose-dependent manner. Reporter gene, electrophoretic mobility shift, kinase inhibitor assays, and in vitro kinase assay showed that ascochlorin inhibits MMP-9 gene expression by suppressing activation of the nuclear transcription factor activator protein-1 (AP-1) via the extracellular signal-regulated kinase 1 and 2 pathway. The AP-1 family member most specifically affected by ascochlorin was Fra-1. Ascochlorin did not affect the activation of the c-Jun N-terminal or p38 kinase pathways. Moreover, transfection of Caki-1 cells with AP-1 decoy oligodeoxynucleotides resulted in the suppression of phorbol 12-myristate 13-acetate-induced MMP-9 expression and invasion. In conclusion, ascochlorin represents a unique natural anti-tumor compound that specifically inhibits MMP-9 activity through suppression of AP-1-dependent induction of MMP-9 gene expression.

Alkenes↗

PubMed2005

8-Hydroxyquinoline inhibits iNOS expression and nitric oxide production by down-regulating LPS-induced activity of NF-kappaB and C/EBPbeta in Raw 264.7 cells.

In activated macrophage, large amounts of nitric oxide (NO) are generated by inducible nitric oxide synthase (iNOS), resulting in acute or chronic inflammatory disorders. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, 8-hydroxyquinoline (8HQ) inhibited the LPS-induced expression of both iNOS protein and mRNA in a parallel dose-dependent manner. 8HQ did not enhance the degradation of iNOS mRNA. To investigate the mechanism by which 8HQ inhibits iNOS gene expression, we examined the activation of MAP kinases in Raw 264.7 cells. We did not observe any significant change in the phosphorylation of MAPKs between LPS alone and LPS plus 8HQ-treated cells. Moreover, 8HQ significantly inhibited the DNA-binding activity of nuclear factor-kappaB (NF-kappaB) and CCAAT/enhancer-binding protein beta (C/EBPbeta), but not activator protein-1 and cAMP response element-binding protein. Taken together, these results suggest that 8HQ acts to inhibit inflammation through inhibition of NO production and iNOS expression through blockade of C/EBPbeta DNA-binding activity and NF-kappaB activation.

Animals↗

PubMed2005

Chrysin suppresses lipopolysaccharide-induced cyclooxygenase-2 expression through the inhibition of nuclear factor for IL-6 (NF-IL6) DNA-binding activity.

Chrysin is a natural, biologically active compound extracted from many plants, honey and propolis. It possesses potent anti-inflammation, anti-cancer and anti-oxidation properties. The mechanism by which chrysin suppresses COX-2 expression remains poorly understood. In the present report, we investigated the effect of chrysin on the expression of COX-2 in lipopolysaccharide (LPS)-activated Raw 264.7 cells. Chrysin significantly suppressed the LPS-induced COX-2 protein and mRNA expression in a dose-dependent manner. The ability of chrysin to suppress the expression of the COX-2 was investigated using luciferase reporters controlled by various cis-elements in COX-2 promoter region. Mutational analysis and electrophoretic mobility shift assay verified that nuclear factor for IL-6 was identified as responsible for the chrysin-mediated COX-2 downregulation. These results will provide new insights into the anti-inflammatory and anti-carcinogenic properties of chrysin.

Animals↗

PubMed2005

LY294002 inhibits LPS-induced NO production through a inhibition of NF-kappaB activation: independent mechanism of phosphatidylinositol 3-kinase.

Phosphatidylinositol 3-kinase (PI3K) is critical player in cell proliferation and survival. The effects of LY294002 and wortmannin, inhibitors of PI3K, on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in lipoploysaccharide (LPS)-induced Raw 264.7 cells were investigated. Significant inhibition of LPS-induced protein kinase B (PKB, Akt) phosphorylation occurred at 25 microM LY294002 or 0.5 microM wortmannin. At the same concentrations, LY294002, but not wortmannin, significantly inhibited NO production and iNOS expression. LY303511, an inactive analogue of LY294002, also inhibited NO production and iNOS expression. In addition, LY294002 and LY303511 significantly inhibited the DNA binding activity of NF-kappaB and NF-kappaB dependent reporter gene expression. These results suggest that LY294002 inhibits iNOS expression at least in part via inhibition of NF-kappaB activation, independent of PI3K.

Androstadienes↗

PubMed2005

Induction of apoptosis and inhibition of cyclooxygenase-2 expression by N-methyl-N'-nitro-N-nitrosoguanidine in human leukemia cells.

Previous studies have demonstrated that N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a well-known DNA alkylating agent, induces G2/M arrest and apoptotic cell death in several human cancer cell lines. In the present study, we investigated the effects of MNNG on the growth of a U937 human leukemia cell model. The effects of this compound were also tested on cyclooxygenase (COX) activity. Treatment of U937 cells with MNNG resulted in the inhibition of viability and the induction of apoptosis in a concentration-dependent manner, which was associated with a dose-dependent upregulation in pro-apoptotic Bax protein, downregulation of anti-apoptotic Bcl-2 and Bcl-xL proteins, and proteolytic activation of caspase-3 protease. Furthermore, MNNG decreased the levels of COX-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with inactivation of the reporter construct of a COX-2 promoter and decrease in prostaglandin E2 synthesis. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of MNNG.

Antineoplastic Agents↗

PubMed2004

Chrysin-induced apoptosis is mediated through caspase activation and Akt inactivation in U937 leukemia cells.

Chrysin is a natural, biologically active compound extracted from many plants, honey, and propolis. It possesses potent anti-inflammation, anti-cancer, and anti-oxidation properties. The mechanism by which chrysin initiates apoptosis remains poorly understood. In the present report, we investigated the effect of chrysin on the apoptotic pathway in U937 human promonocytic cells. We show that chrysin induces apoptosis in association with the activation of caspase 3 and that Akt signal pathway plays a crucial role in chrysin-induced apoptosis in U937 cells. Furthermore, we have shown that inhibition of Akt phosphorylation in U937 cells by the specific PI3K inhibitor, LY294002 significantly, enhanced apoptosis. Overexpression of a constitutively active Akt (myr-Akt) in U937 cells inhibited the induction of apoptosis, activation of caspase 3, and PLC-gamma1 cleavage by chrysin. Together, these findings suggest that the Akt pathway plays a major role in regulating the apoptotic response of human leukemia cells to chrysin and raise the possibility that combined interruption of chrysin and PI3K/Akt-related pathways may represent a novel therapeutic strategy in hematological malignancies.

Apoptosis↗

PubMed2004

Catalase induces the expression of inducible nitric oxide synthase through activation of NF-kappaB and PI3K signaling pathway in Raw 264.7 cells.

It has been reported that macrophages produce substantial amounts of nitrite and nitrate after addition of catalase, but the mechanism associated remains unclear. In present study, we investigated whether catalase modulates the expression of inducible nitric oxide synthase (iNOS), an enzyme that produces nitric oxide. Exposure of Raw 264.7 macrophages (Raw cells) to catalase induced high expression of iNOS mRNA as well as protein with enzymatic activity. Data of mechanical analyses, such as iNOS promoter-driven luciferase assay and actinomycin D chase experiments demonstrated that the induction was due to increased iNOS transcription and post-transcriptional iNOS mRNA stability. Of interest, catalase-induced iNOS protein expression was abrogated through inactivation of NF-kappaB pathway by MG132 or BAY 11-7085 and PI3K pathway by LY294002 or wortmannin, respectively. In particular, blockage of PI3K pathway by LY294002 down-regulated iNOS transcription and steady-state iNOS mRNA levels as well as iNOS mRNA stability induced by catalase, suggesting regulation of PI3K pathway in catalase-induced iNOS expression at the levels of iNOS transcription, steady-state mRNA status, and mRNA stability. Additional cell culture works in different types of cells indicated that iNOS expression by catalase might be cell type-specific, based on the facts that catalase induced iNOS expression in BV2 microglial macrophage-like cells, but not in HT-29 or A549, human colon or lung cancer epithelial-like cells. Together, these results demonstrate for the first time that catalase induces iNOS expression in Raw cells, which seems to be associated with the increase of iNOS transcription and mRNA stability as well as the activation of NF-kappaB and PI3K signaling pathways.

Animals↗

PubMed2004

Ciglitizone inhibits cell proliferation in human uterine leiomyoma via activation of store-operated Ca2+ channels.

This study investigated the acute effects of a peroxisome proliferator-activated receptor (PPAR)-gamma ligand, ciglitizone, on cell proliferation and intracellular Ca2+ signaling in human normal myometrium and uterine leiomyoma. Changes in intracellular Ca2+ concentration ([Ca2+]i) were measured with fura-2 AM, and cellular viabilities were determined by viable cell count and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction assay. Ciglitizone (100 microM) induced greater inhibition of cell proliferation in uterine leiomyoma than in myometrium. Ciglitizone also dose-dependently increased [Ca2+]i in both myometrium and uterine leiomyoma; these [Ca2+]i increases were inhibited by PPAR-gamma antagonists and raloxifene. Ciglitizone-induced [Ca2+]i increase showed only an initial peak in normal myometrial cells, whereas in uterine leiomyoma there was a second sustained [Ca2+]i increase as well. The initial [Ca2+]i increase in both myometrium and uterine leiomyoma resulted from the release of Ca2+ by the sarcoplasmic reticulum via activation of ryanodine receptors. The second [Ca2+]i increase was observed only in uterine leiomyoma because of a Ca2+ influx via an activation of store-operated Ca2+ channels (SOCCs). Cell proliferation was inhibited and secondary [Ca2+]i increase in uterine leiomyoma was attenuated by cotreatment of ciglitizone with a SOCC blocker, lanthanum. The results suggest that ciglitizone inhibits cell proliferation and increases [Ca2+]i through the activation of SOCCs, especially in human uterine leiomyoma.

Calcium↗

PubMed2004

Up-regulation of human beta-defensin 2 by interleukin-1beta in A549 cells: involvement of PI3K, PKC, p38 MAPK, JNK, and NF-kappaB.

Induction of human beta-defensin 2 (HBD-2) by interleukin-1beta (IL-1beta) in epithelial cells has been reported. However, the mechanism by which IL-1beta up-regulates HBD-2 remains poorly understood. In this study, we investigated the effect of IL-1beta on induction of HBD-2 in A549 cells. IL-1beta markedly increased HBD-2 mRNA expression in concentration- and time-dependent manners. HBD-2 mRNA expression in response to IL-1beta was attenuated by pretreatment of GF109203X, Go6976, and staurosporine [inhibitors of protein kinase C (PKC)], SB203580 [an inhibitor of p38 mitogen-activated protein kinase (MAPK)], SP600125 [an inhibitor of c-Jun N-terminal kinase (JNK)], and LY294002 [an inhibitor of phosphatidylinositol-3-kinase (PI3K)], but not PD98059 [an inhibitor of extracellular signal-regulated kinase (ERK)], suggesting involvement of PKC, p38 MAPK, JNK, and PI3K in this response. Interestingly, IL-1beta induced nuclear factor-kappaB (NF-kappaB) activation in A549 cells, which was shown by increased nuclear translocation of p65 NF-kappaB and degradation of IkappaB-alpha. Importantly, IL-1beta-induced HBD-2 mRNA expression was inhibited by blockage of NF-kappaB activation using NF-kappaB inhibitors, including pyrrolidine dithiocarbamate and MG132. Specifically, IL-1beta-induced nuclear translocation of NF-kappaB was in part attenuated by LY294002, but not by GF109203X, SB203580, and SP600125, suggesting PI3K-dependent nuclear translocation of NF-kappaB in response to IL-1beta. Together, these results suggest that IL-1beta induces HBD-2 mRNA expression in A549 cells, and the induction seems to be at least in part mediated through activation of NF-kappaB transcription factor as well as activation of signaling proteins of PKC, p38 MAPK, JNK, and PI3K, but not ERK.

Adenocarcinoma↗

PubMed2004

Leptomycin B-induced apoptosis is mediated through caspase activation and down-regulation of Mcl-1 and XIAP expression, but not through the generation of ROS in U937 leukemia cells.

Leptomycin B (LMB), which is originally isolated from Streptomyces, possesses anti-tumor properties in vivo and in vitro. Though it was previously reported that LMB induces cell cycle arrest and p53-mediated apoptosis in certain cancer cells, however, the mechanism by which LMB induces apoptosis remains poorly understood. Here, we investigated the mechanisms of apoptosis induced by LMB in U937 cells. Treatment with LMB concentration-dependently induced cytotoxicity and apoptosis in U937 cells that correlated temporally with activation of caspases and down-regulation of Mcl-1 and XIAP. LMB did not change the expressions of Bcl-2 or Bax. A broad spectrum caspase inhibitor, z-VAD-fmk, blocked caspase-3 activation and elevated the survival in LMB-treated U937 cells, suggesting that caspase-3 activation is critical for LMB-induced apoptosis. Interestingly, Bcl-2 overexpression that blocked cytochrome c release by LMB effectively attenuated the apoptotic response to LMB, suggesting that LMB-induced apoptosis is mediated through the mitochondrial pathway. Antioxidants or antioxidant enzymes had no effects on LMB-induced apoptosis. Data of flow cytometry analysis using 2',7'-dichlorofluorescein-diacetate further revealed no reactive oxygen species (ROS) generation by LMB, indicating that apoptosis induced by LMB is ROS-independent. However, the apoptotic response to LMB was not shown in U937 cells pretreated with the sulfhydryl group-containing antioxidant N-acetylcysteine (NAC). Further analysis suggested that NAC directly binds LMB and abolishes the apoptotic effects of LMB. Collectively, these findings suggest that LMB potently induces apoptosis in U937 cells, and LMB-induced apoptosis in U937 cells is related with cytochrome c release, activation of caspases, and selective down-regulation of Mcl-1 and XIAP.

Antibiotics, Antineoplastic↗

PubMed2004

Triptolide inhibits murine-inducible nitric oxide synthase expression by down-regulating lipopolysaccharide-induced activity of nuclear factor-kappa B and c-Jun NH2-terminal kinase.

Triptolide (PG490) is a natural, biologically active compound extracted from the Chinese herb Tripterygium wilfordii. It has been shown to possess potent anti-inflammatory and immunosuppressive properties. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, triptolide inhibits nitric oxide (NO) production in a dose-dependent manner and abrogates inducible nitric oxide synthase (iNOS) gene expression. To investigate the mechanism by which triptolide inhibits murine iNOS gene expression, we examined activation of mitogen-activated protein kinases (MAP kinases) and nuclear factor-kappa B (NF-kappa B) in these cells. Addition of triptolide inhibited phosphorylation of c-Jun NH(2)-terminal kinase (JNK) but not that of extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein kinase. In addition, triptolide significantly inhibited the DNA binding activity of NF-kappa B. Taken together, these results suggest that triptolide acts to inhibit inflammation through inhibition of NO production and iNOS expression through blockade of NF-kappa B and JNK activation.

Animals↗

PubMed2004

Transcriptional repression of E2F gene by proteasome inhibitors in human osteosarcoma cells.

E2F family of transcription factors regulates the transcription of genes required for DNA synthesis. E2F is itself controlled by a series of transcriptional and post-transcriptional pathways. Here we provide evidence that proteasome inhibitor-mediated E2F1 gene down-regulation is regulated by transcriptional events. Using the proteasome-specific inhibitors, MG132 and lactacystin, we show that the p53, the cdk inhibitors p21 and p27, and cyclin A are degraded by the ubiquitin-proteasome pathway in human osteosarcoma cells. Interestingly, the expression levels of E2F1 and E2F2 are down-regulated by proteasome inhibitors. E2F promoter and RT-PCR assay clearly demonstrated that proteasome inhibitors could reduce E2F transcriptional activation. However, MG132-induced repression of E2F1 and E2F2 is not associated with ROS generation.

Acetylcysteine↗

PubMed2004

Sodium butyrate sensitizes TRAIL-mediated apoptosis by induction of transcription from the DR5 gene promoter through Sp1 sites in colon cancer cells.

Sodium butyrate, a short-chain fatty acid naturally present in the human colon, is able to induce cell cycle arrest, differentiation and apoptosis in various cancer cells. Sodium butyrate is most probably related to the inhibition of deacetylases leading to hyperacetylation of chromatin components such as histones and non-histone proteins and to alterations in gene expression. In this study, we demonstrate for the first time that sodium butyrate selectively up-regulated DR5 but had no effect on the expression of the other TNF-alpha-related apoptosis-inducing ligand (TRAIL) receptor, DR4. Sodium butyrate-induced expression of DR5 involves the putative Sp1 site within the DR5 promoter region. Using a combination of the electrophoretic mobility shift assay and the luciferase reporter assay, we found that a specific Sp1 site (located at -195 bp relative to the transcription start site) is required for sodium butyrate-mediated activation of the DR5 promoter. When HCT116 cells were incubated with sodium butyrate and TRAIL, enhanced TRAIL-mediated apoptosis was observed. The enhanced apoptosis was measured by fluorescent activated cell sorting analysis, DNA fragmentation, poly (ADP-ribose) polymerase cleavage, down-regulation of XIAP and caspase activity. Taken together, the present studies suggest that sodium butyrate may be an effective sensitizer of TRAIL-induced apoptosis.

Apoptosis↗

PubMed2004

Induction of cyclooxygenase-2 in macrophages by catalase: role of NF-kappaB and PI3K signaling pathways.

Induction of COX-2 by catalase in smooth muscle cells, endothelial cells, and neuronal cells has been previously reported. However, the mechanism by which catalase up-regulates COX-2 remains poorly understood. In this study, we investigated the effect of catalase on induction of COX-2 in macrophages. The addition of catalase into Raw 264.7 macrophages induced COX-2 expression that was correlated with increased COX-2 transcription and mRNA stability. Catalase also induced activation of NF-kappaB, PI3K, ERKs, p38s, or JNKs. Catalase-induced COX-2 expression was abrogated by treatment of MG-132 (a NF-kappaB inhibitor) or LY294002 (a PI3K inhibitor), but not by treatment of PD98059 (an ERK inhibitor), SB203580 (a p38 inhibitor), or SP600125 (a JNK inhibitor). Moreover, inhibition of PI3K by LY294002 caused partial decrease of catalase-induced COX-2 transcription and steady-state COX-2 transcript levels, but not COX-2 mRNA stability. Together, these results suggest that catalase induces the expression of COX-2 in Raw 264.7 macrophages, and the induction is related with activation of NF-kappaB transcription factor and PI3K signaling pathway.

Animals↗

PubMed2004

Inhibition of ATP-sensitive K+ channels by taurine through a benzamido-binding site on sulfonylurea receptor 1.

ATP-sensitive potassium (K(ATP)) channels in pancreatic beta-cells comprise sulfonylurea receptor (SUR) 1 and inwardly-rectifying potassium channel (Kir) 6.2 subunits. We have evaluated the effect of intracellular taurine on K(ATP) channel activity in rat pancreatic beta-cells using the patch-clamp technique. The mechanism of taurine action was also examined using recombinant K(ATP) channels. The islets and single beta-cells from male Sprague-Dawley rats were collected by collagenase digestion technique. Single K(ATP) channel currents were recorded by the inside-out mode at a membrane potential of -60mV. Cytosolic free-Ca(2+) concentration ([Ca(2+)](c)) and insulin secretory capacity were measured by the dual-excitation fluorimetry and radioimmunoassay, respectively. The native beta-cell K(ATP) channel was directly inhibited by taurine in a dose-dependent manner. Taurine did not influence ATP-mediated inhibition or MgADP-induced activation of the channel activity. The sensitivity of the K(ATP) channel to glybenclamide, but not gliclazide, was enhanced by taurine. Glybenclamide elicited a greater increase in [Ca(2+)](c) and increased insulin secretion in the beta-cells when pretreated with taurine. Taurine did not inhibit Kir6.2DeltaC36 currents, a truncated form of Kir6.2, expressed in Xenopus oocytes without SUR. These results demonstrate that taurine inhibits the K(ATP) channel activity in the beta-cells, interacting with a benzamido-binding site on SUR1, but not Kir6.2.

Adenosine Diphosphate↗