Irsogladine upregulates expressions of connexin32 and connexin26 in the rat liver

Nakashima, Yuichi; Kohno, Hitoshi; El-Assal, Osama N.; Dhar, Dipok Kumar; Ueda, Fusao; Nagasue, Naofumi

doi:10.1016/s1386-6346(99)00082-0

Cited by 8 publications

(6 citation statements)

References 34 publications

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“…Previous studies documented that the effects of IM and NO on Cx43 levels are mediated by cAMP signaling ( Nakashima et al ., 2000 ; Kawasaki et al ., 2002 ; Yao et al ., 2005 ). The cooperative induction of Cx43 suggests that IM and NO may additively activate cAMP signal pathway.…”

Section: Resultsmentioning

confidence: 99%

“…Given that the levels of GJ proteins are reversibly correlated with cell proliferation ( Goodenough et al ., 1996 ; Kumar and Gilula, 1996 ) and that both IM and NO are known stimulators of connexin Cx43 expression ( Nakashima et al ., 2000 ; Kawasaki et al ., 2002 ; Yao et al ., 2005 ), we therefore examined the induction of Cx43 by these agents in mesangial cells. As shown in Figure 2, incubation of mesangial cells with SNAP caused a concentration‐dependent elevation in Cx43 level.…”

Section: Resultsmentioning

confidence: 99%

“…IM induces expression of several different GJ proteins, including connexin26, 32 and 43. This effect of IM is mediated by cAMP signaling ( Nakashima et al ., 2000 ; Kawasaki et al ., 2002 ; Uchida et al ., 2005 ). More recently, IM has been characterized as an inhibitor of phosphodiesterase 4 (PDE4) ( Kyoi et al ., 2004a , 2004b ), a predominant cAMP‐degrading enzyme present in various cell types ( Beavo, 1995 ; Dousa, 1999 ).…”

Section: Introductionmentioning

confidence: 99%

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Irsogladine maleate potentiates the effects of nitric oxide on activation of cAMP signalling pathways and suppression of mesangial cell mitogenesis

Yao

Zhu

Sun

et al. 2007

British J Pharmacology

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Background and purpose: Deficiency in nitric oxide (NO) is a major factor leading to deterioration and progression of certain glomerular diseases. Agents enhancing NO availability and potentiality are renoprotective. Irsogladine maleate (IM), an antiulcer drug, is reported to improve gastric blood flow via NO-dependent mechanisms. We, therefore, asked whether and how IM interacted with NO on glomerular mesangial cells. Experimental approach: Mesangial cells were exposed to IM and NO donors. Activation of cAMP signalling pathways was assessed by intracellular cAMP, phosphorylation of VASP, activation of the cAMP response element (CRE) and expression of CRE-regulated proteins. Key results: IM alone did not affect cell proliferation. However, it greatly enhanced the growth-inhibitory effect of NO donor S-nitroso-N-acetylpenicillamine (SNAP). IM acted synergistically with NO on suppression of mitogen-activated protein kinase activation, induction of gap junction protein connexin43, increase of intracellular cAMP, and phosphorylation of VASP. With the use of the CRE-SEAP-based reporting system, IM and SNAP cooperatively activated cAMP response elements (CRE). A similar activation of cAMP was induced by IM with two different NO donors, the sGC activator Bay 41-2272 and the cGMP analogue 8-bromo-cGMP. The effects of SNAP and IM on cAMP activation were mimicked by phosphodiesterase 3 (PDE3) and PDE4 inhibitors. In addition, IM markedly augmented cytokine-induced expression of iNOS, production of NO and activation of CRE. Conclusion and implications:The effects of NO were greatly potentiated by IM through synergistic activation of cAMP pathway. Combined therapy with IM and NO may be developed for certain renal diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Irsogladine maleate potentiates the effects of nitric oxide on activation of cAMP signalling pathways and suppression of mesangial cell mitogenesis

Yao

Zhu

Sun

et al. 2007

British J Pharmacology

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“…actinomycetemcomitans Y4 at 1 x 10 8 cells/ml or IL-8 at 10 ng/ml in the absence or presence of IM at 1 μM or mouse anti-human CXCR-1 antibody at 0.3 μg/ml in 5 ml of medium B for 12 h. Microinjection of a 10% Lucifer yellow CH (Sigma) solution in 1 M LiCl into HGEC under a phase-contrast microscope was carried out by a method described previously [12]. Five minutes after the microinjection, the extent of the dye's transfer was recorded under a fluorescence microscope (Nikon, Tokyo, Japan).…”

Section: Measurement Of Gjic Between Hgecmentioning

confidence: 99%

Regulation of IL-8 by Irsogladine maleate is involved in abolishment of Actinobacillus actinomycetemcomitans-induced reduction of gap-junctional intercellular communication

et al. 2006

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Our previous report has shown that Irsogladine maleate (IM) counters and obviates the reduction in gap junction intercellular communication (GJIC) and the increase in IL-8 levels, respectively, induced by outer membrane protein 29 from Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) in cultured human gingival epithelial cells (HGEC). In addition, IM suppresses the increase in the secretion of IL-8 caused by whole live A. actinomycetemcomitans. These findings implicate the modulation of IL-8 levels by IM in abolishment of the reduction of GJIC in HGEC. Tight junctions are also responsible for cell-cell communication. Zonula occludens protein-1 (ZO-1) is a major tight junction protein. To investigate the regulatory mechanism of intercellular communication mediated by IM, in the present study, we focused on the involvement of IL-8 in A. actinomycetemcomitans-induced change in GJIC and ZO-1 expression in HGEC. IM countered the A. actinomycetemcomitans-induced reduction in levels of Connexin (CX) 43, suggesting that it could abolish the A. actinomycetemcomitans-induced reduction in GJIC in HGEC. CXCR-1 is a receptor of IL-8. The simultaneous addition of A. actinomycetemcomitans and anti-CXCR-1 antibody also abrogated the repression of GJIC and CX43 expression by A. actinomycetemcomitans in HGEC, although the anti-CXCR-1 antibody was less effective than IM. IM inhibited the IL-8-induced reduction in CX43 levels and GJIC in HGEC. IM countered the A. actinomycetemcomitans-induced reduction in the expression of ZO-1, although anti-CXCR-1 antibody did not influence the decrease in ZO-1 mRNA levels caused by A. actinomycetemcomitans. Furthermore, IL-8 had little effect on the mRNA levels of ZO-1. These findings suggest that IL-8 mediates the A. actinomycetemcomitans-induced reduction of GJIC and CX43 expression in HGEC. The regulation of IL-8 levels by IM in HGEC is partially involved in abrogation of the reduction of GJIC and CX43 expression by A. actinomycetemcomitans. Furthermore, the regulatory effect of IM on the expression of CX43 and ZO-1 is different.

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“…Irsogladine maleate (IM) enhances gap junction intercellular communication in cultured rabbit gastric epithelial cells and pancreatic cancer cells through augmentation of the cyclic AMP (7,8). In addition, IM increases levels of connexin 32, which is related to the repair of gastric ulcers (9). IM has been used clinically as an anti‐gastric ulcer agent.…”

mentioning

confidence: 99%

Irsogladine maleate abolishes the increase in interleukin‐8 levels caused by outer membrane protein 29 from Aggregatibacter (Actinobacillus) actinomycetemcomitans through the ERK pathway in human gingival epithelial cells

Kishimoto

Fujita

Shiba

et al. 2008

J of Periodontal Research

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Irsogladine upregulates expressions of connexin32 and connexin26 in the rat liver

Cited by 8 publications

References 34 publications

Irsogladine maleate potentiates the effects of nitric oxide on activation of cAMP signalling pathways and suppression of mesangial cell mitogenesis

Irsogladine maleate potentiates the effects of nitric oxide on activation of cAMP signalling pathways and suppression of mesangial cell mitogenesis

Regulation of IL-8 by Irsogladine maleate is involved in abolishment of Actinobacillus actinomycetemcomitans-induced reduction of gap-junctional intercellular communication

Irsogladine maleate abolishes the increase in interleukin‐8 levels caused by outer membrane protein 29 from Aggregatibacter (Actinobacillus) actinomycetemcomitans through the ERK pathway in human gingival epithelial cells

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