共查询到12条相似文献,搜索用时 0 毫秒
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H.S. Cheng P.Y. Leung S.B. Cheng Chew P.S. Leung S.Y. Lam W.S. Wong Z.D. Wang H.C. Chan 《The Journal of membrane biology》1998,164(2):155-167
The present study investigated both HCO−
3 and Cl− secretions in a human pancreatic duct cell line, CAPAN-1, using the short-circuit current (I
sc
) technique. In Cl−/HCO−
3-containing solution, secretin (1 μm) or forskolin (10 μm) stimulated a biphasic rise in the I
sc
which initially reached a peak level at about 3 min and then decayed to a plateau level after 7 min. Removal of external
Cl− abolished the initial transient phase in the forskolin-induced I
sc
while the plateau remained. In HCO−
3/CO2-free solution, on the contrary, only the initial transient increase in I
sc
was prominent. Summation of the current magnitudes observed in Cl−-free and HCO−
3-free solutions over a time course of 10 min gave rise to a curve which was similar, both in magnitude and kinetics, to the
current observed in Cl−/HCO−
3-containing solution. Removal of external Na+ greatly reduced the initial transient rise in the forskolin-induced I
sc
response, and the plateau level observed under this condition was similar to that obtained in Cl−-free solution, suggesting that Cl−-dependent I
sc
was also Na+-dependent. Bumetanide (50 μm), an inhibitor of the Na+-K+-2Cl− cotransporter, and Ba2+ (1 mm), a K+ channel blocker, could reduce the forskolin-induced I
sc
obtained in Cl−/HCO−
3-containing or HCO−
3-free solution. However, they were found to be ineffective when external Cl− was removed, indicating the involvement of these mechanisms in Cl− secretion. On the contrary, the HCO−
3-dependent (in the absence of external Cl−) forskolin-induced I
sc
could be significantly reduced by carbonic anhydrase inhibitor, acetazolamide (45 μm). Basolateral application of amiloride (100 μm) inhibited the I
sc
; however, a specific Na+-H+ exchanger blocker, 5-N-methyl-N-isobutylamiloride (MIA, 5–10 μm) was found to be ineffective, excluding the involvement of
the Na+-H+ exchanger. However, an inhibitor of H+-ATPase, N-ethylmaleimide did suppress the I
sc
(IC50= 22 μm). Immunohistochemical studies also confirmed the presence of a vacuolar type of H+-ATPase in these cells. H2DIDS (100 μm), an inhibitor of Na+-HCO−
3 cotransporter, was without effect. Apical addition of Cl− channel blocker, diphenylamine-2,2′-dicarboxylic acid (DPC, 1 mm), but not disulfonic acids, DIDS (100 μm) or SITS (100 μm), exerted an inhibitory effect on both Cl− and HCO−
3-dependent forskolin-induced I
sc
responses. Histochemical studies showed discrete stainings of carbonic anhydrase in the monolayer of CAPAN-1 cells, suggesting
that HCO−
3 secretion may be specialized to a certain population of cells. The present results suggest that both HCO−
3 and Cl− secretion by the human pancreatic duct cells may occur concurrently and independently.
Received: 17 October 1997/Revised: 3 April 1998 相似文献
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Jun Qin Ni Fang Jinning Lou Wenjian Zhang Shiqing Xu Honglin Liu Qing Fang Zai Wang Jiang Liu Xiuli Men Liang Peng Li Chen 《PloS one》2014,9(5)
Chronic exposure to free fatty acids (FFAs) may induce β cell apoptosis in type 2 diabetes. However, the precise mechanism by which FFAs trigger β cell apoptosis is still unclear. Tribbles homolog 3 (TRB3) is a pseudokinase inhibiting Akt, a key mediator of insulin signaling, and contributes to insulin resistance in insulin target tissues. This paper outlined the role of TRB3 in FFAs-induced INS-1 β cell apoptosis. TRB3 was promptly induced in INS-1 cells after stimulation by FFAs, and this was accompanied by enhanced INS-1 cell apoptosis. The overexpression of TRB3 led to exacerbated apoptosis triggered by FFAs in INS-1-derived cell line and the subrenal capsular transplantation animal model. In contrast, cell apoptosis induced by FFAs was attenuated when TRB3 was knocked down. Moreover, we observed that activation and nuclear accumulation of protein kinase C (PKC) δ was enhanced by upregulation of TRB3. Preventing PKCδ nuclear translocation and PKCδ selective antagonist both significantly lessened the pro-apoptotic effect. These findings suggest that TRB3 was involved in lipoapoptosis of INS-1 β cell, and thus could be an attractive pharmacological target in the prevention and treatment of T2DM. 相似文献
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Deepak Chatterjee Areetha D’Souza Yaming Zhang Wu Bin Suet-Mien Tan Surajit Bhattacharjya 《Journal of molecular biology》2018,430(21):4419-4430
Integrins are hetero-dimeric (α and β subunits) type I transmembrane proteins that facilitate cell adhesion and migration. The cytoplasmic tails (CTs) of integrins interact with a plethora of intra-cellular proteins that are required for integrin bidirectional signaling. In particular, the β CTs of integrins are known to recruit a variety of cytosolic proteins that often have overlapping recognition sites. However, the chronological sequence of β CTs/cytosolic proteins interactions remains to be fully characterized. Previous studies have shown that the scaffold protein 14-3-3ζ binds to phosphorylated β CTs in activated integrins, whereas interactions of Dok-1 with phosphorylated β CTs maintained integrins in the resting state. In this study, we examined the binding interactions between 14-3-3ζ, Dok1, and phosphorylated integrin β2 and β3 CTs. We show that the scaffold protein 14-3-3ζ interacts with the phosphotyrosine binding (PTB) domain of Dok1 even in the absence of the phosphorylated integrin β CTs. The interactions were mapped onto the β-sheet region of the PTB domain of Dok1. Furthermore, we provide evidence that the 14-3-3ζ/Dok1 binary complex is able to bind to their cognate phosphorylated sequence motifs in the integrin β CTs. We demonstrate that Thr phosphorylated pTTT β2 CT or pTST β3 CT can bind to 14-3-3ζ that is in complex with the Dok1 PTB domain, whereas Ser phosphorylated β2 CT or Tyr phosphorylated β3 CT interacted with Dok1 in 14-3-3ζ/Dok1 complex. Based on these data, we propose that 14-3-3ζ/Dok1 complex could serve as a molecular switch providing novel molecular insights into the regulating integrin activation. 相似文献
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The translocation and accumulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the nucleus has closely been associated with cell death induction. However, the mechanism of this process has not been completely understood. The E3 ubiquitin ligase siah-1 (seven in absentia homolog 1) has recently been identified as a potential shuttle protein to transport GAPDH from the cytosol to the nucleus. Previously, we have demonstrated that elevated glucose levels induce GAPDH nuclear accumulation in retinal Müller cells. Therefore, this study investigated the role of siah-1 in high glucose-induced GAPDH nuclear translocation and subsequent cell death in retinal Müller cells. High glucose significantly increased siah-1 expression within 12 h. Under hyperglycemic conditions, siah-1 formed a complex with GAPDH and was predominantly localized in the nucleus of Müller cells. siah-1 knockdown using 50 nm siah-1 small interfering RNA significantly decreased high glucose-induced GAPDH nuclear accumulation at 24 h by 43.8 ± 4.0%. Further, knockdown of siah-1 prevented high glucose-induced cell death of Müller cells potentially by inhibiting p53 phosphorylation consistent with previous observations, indicating that nuclear GAPDH induces cell death via p53 activation. Therefore, inhibition of GAPDH nuclear translocation and accumulation by targeting siah-1 promotes Müller cell survival under hyperglycemic conditions. 相似文献
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Ting Wu Yuanyue Li Deli Huang Felicia Han Ying-Ying Zhang Duan-Wu Zhang Jiahuai Han 《PloS one》2014,9(4)
Autophagy has diverse biological functions and is involved in many biological processes. The L929 cell death induced by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-(OMe)-fluoromethyl ketone (zVAD) was shown to be an autophagy-mediated death for which RIP1 and RIP3 were both required. It was also reported that zVAD can induce a small amount of TNF production, which was shown to be required for zVAD-induced L929 cell death, arguing for the contribution of autophagy in the zVAD-induced L929 cell death. In an effort to study RIP3 mediated cell death, we identified regulator of G-protein signaling 19 (RGS19) as a RIP3 interacting protein. We showed that RGS19 and its partner Gα-inhibiting activity polypeptide 3 (GNAI3) are involved in zVAD-, but not TNF-, induced cell death. The role of RGS19 and GNAI3 in zVAD-induced cell death is that they are involved in zVAD-induced autophagy. By the use of small hairpin RNAs and chemical inhibitors, we further demonstrated that zVAD-induced autophagy requires not only RIP1, RIP3, PI3KC3 and Beclin-1, but also RGS19 and GNAI3, and this autophagy is required for zVAD-induced TNF production. Collectively, our data suggest that zVAD-induced L929 cell death is a synergistic result of autophagy, caspase inhibition and autocrine effect of TNF. 相似文献
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Soniya Dhanjal Naoko Kajitani Jacob Glahder Ann-Kristin Mossberg Cecilia Johansson Stefan Schwartz 《The Journal of biological chemistry》2015,290(21):13354-13371
In order to identify cellular factors that regulate human papillomavirus type 16 (HPV16) gene expression, cervical cancer cells permissive for HPV16 late gene expression were identified and characterized. These cells either contained a novel spliced variant of the L1 mRNAs that bypassed the suppressed HPV16 late, 5′-splice site SD3632; produced elevated levels of RNA-binding proteins SRSF1 (ASF/SF2), SRSF9 (SRp30c), and HuR that are known to regulate HPV16 late gene expression; or were shown by a gene expression array analysis to overexpress the RALYL RNA-binding protein of the heterogeneous nuclear ribonucleoprotein C (hnRNP C) family. Overexpression of RALYL or hnRNP C1 induced HPV16 late gene expression from HPV16 subgenomic plasmids and from episomal forms of the full-length HPV16 genome. This induction was dependent on the HPV16 early untranslated region. Binding of hnRNP C1 to the HPV16 early, untranslated region activated HPV16 late 5′-splice site SD3632 and resulted in production of HPV16 L1 mRNAs. Our results suggested that hnRNP C1 controls HPV16 late gene expression. 相似文献
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