Publications (5)9.66 Total impact
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Article: Adrenomedullin in sinusoidal endothelial cells play protective roles against cold injury of liver.
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ABSTRACT: Donor organ damage caused by cold preservation is a major problem affecting liver transplantation. Cold preservation most easily damages liver sinusoidal endothelial cells (LSECs), and information about the molecules modulating LSECs function can provide the basis for new therapeutic strategies. Adrenomedullin (AM) is a peptide known to possess anti-apoptotic and anti-inflammatory properties. AM is abundant in vascular endothelial cells, but levels are comparatively low in liver, and little is known about its function there. In this study, we demonstrated both AM and its receptors are expressed in LSECs. AM treatment reduced LSECs loss and apoptosis under cold treatment. AM also downregulated cold-induced expression of TNFalpha, IL1beta, IL6, ICAM1 and VCAM1. AM reduced apoptosis and expression of ICAM1 and VCAM1 in an in vivo liver model subjected to cold storage. Conversely, apoptosis was exacerbated in livers from AM and RAMP2 (AM receptor activity-modifying protein) knockout mice. These results suggest that AM expressed in LSECs exerts a protective effect against cold-organ damage through modulation of apoptosis and inflammation.Peptides 05/2010; 31(5):865-71. · 2.43 Impact Factor -
Article: Endogenous alpha-calcitonin gene-related peptide mitigates liver fibrosis in chronic hepatitis induced by repeated administration of concanavalin A.
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ABSTRACT: Alpha-calcitonin gene-related peptide (alphaCGRP) is a 37-amino acid pleiotropic peptide that we previously showed to exert a hepatoprotective effect during concanavalin A (Con A)-induced acute hepatitis. In the present study, we used alphaCGRP(-/-) mice to further investigate the antifibrogenic and hepatoprotective effects of endogenous alphaCGRP in Con A-induced chronic hepatitis. Chronic hepatitis was induced in alphaCGRP(-/-) and wild-type mice by repeated administration of Con A. Serum transaminases were measured to assess hepatic injury. The severity of fibrosis and the activation of hepatic stellate cells (HSCs) were analysed by Masson trichrome staining and immunohistochemical staining of alpha-smooth muscle actin (alpha-SMA) respectively. Altered expression of fibrosis- and inflammation-related genes was evaluated using a quantitative real-time polymerase chain reaction. Activation and proliferation of HSCs were analysed using both primary cultured HSCs from the mice and the LI90 HSC cell line. alphaCGRP(-/-) mice showed more severe liver fibrosis than wild-type mice in a Con A-induced chronic hepatitis model. In histological and gene expression analyses, alphaCGRP(-/-) mice showed greater inflammatory and fibrotic changes, greater HSC activation and a higher incidence of apoptosis among nonparenchymal cells than wild-type mice. Endogenous alphaCGRP mitigates liver fibrosis in chronic hepatitis induced by repeated administration of Con A. alphaCGRP could be a useful therapeutic target for the treatment of chronic hepatitis.Liver international: official journal of the International Association for the Study of the Liver 08/2008; 29(5):642-9. · 3.82 Impact Factor -
Article: Endogenous alphaCGRP protects against concanavalin A-induced hepatitis in mice.
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ABSTRACT: To evaluate hepatoprotective effect of alpha-calcitonin gene-related peptide (alphaCGRP), we compared the susceptibilities of alphaCGRP-/- and wild-type mice to concanavalin A (Con A)-induced hepatitis. Twelve hours after Con A administration, serum transaminases were markedly higher in alphaCGRP-/- than wild-type mice, and much more extensive TUNEL-positive lesions and DNA fragmentation were detected in the livers of alphaCGRP-/- mice. Notably, expression of IL-6 was selectively diminished in alphaCGRP-/- mice, suggesting that induction of IL-6 during acute inflammatory responses is blunted in alphaCGRP-/- mice. In addition, primary cultured alphaCGRP-/- hepatocytes were more susceptible to IFN-gamma-induced cell death than hepatocytes from wild-type mice. Administration of exogenous alphaCGRP reduced the incidence of apoptosis among hepatocytes and endothelial cells. It thus appears that alphaCGRP exerts a hepatoprotective effect by modulating cytokine expression and preventing apoptosis.Biochemical and Biophysical Research Communications 05/2006; 343(1):152-8. · 2.48 Impact Factor -
Article: Liver protection by bis(maltolato)zinc(II) complex.
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ABSTRACT: The aim of this study was to perform screening of a novel drug for treating liver injury. Bis(maltolato)zinc(II) complex [Zn(Mal)(2)], which was previously reported to possess insulinomimetic activity, was found to have potency against experimentally induced liver injury both in vitro and in vivo. Cultured rat hepatocytes were treated with bromobenzene for 24 h to induce cellular injury. Zn(Mal)(2) of various concentrations was added along with bromobenzene in order to evaluate the hepatoprotective activity of Zn(Mal)(2) in vitro. The number of viable hepatocytes decreased by 42% in the culture with bromobenzene. However, hepatocyte viability was maintained when Zn(Mal)(2) was added to the bromobenzene culture. The hepatoprotective activity of Zn(Mal)(2) in vivo was investigated using a concanavalin A-induced liver injury model in BALB/c mice. Changes in serum aminotransferase activities and the secretion of several cytokines were measured. The hepatoprotective effect of Zn(Mal)(2) was also demonstrated in vivo by the suppression of serum aspartate aminotransferase and alanine aminotransferase elevation. No significant changes in serum cytokines associated with the induction of hepatic damage were observed in the concanavalin A-induced injury model. However, examination of concanavalin A-treated mouse splenocytes revealed a dose-dependent suppression of cytokine secretions by Zn(Mal)(2). Zn(Mal)(2) possessed hepatoprotective activity and might exert its effect by a number of mechanisms.Experimental Animals 02/2004; 53(1):1-9. · 0.92 Impact Factor -
Article: Endogenous αCGRP protects against concanavalin A-induced hepatitis in mice
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ABSTRACT: To evaluate hepatoprotective effect of α-calcitonin gene-related peptide (αCGRP), we compared the susceptibilities of αCGRP−/− and wild-type mice to concanavalin A (Con A)-induced hepatitis. Twelve hours after Con A administration, serum transaminases were markedly higher in αCGRP−/− than wild-type mice, and much more extensive TUNEL-positive lesions and DNA fragmentation were detected in the livers of αCGRP−/− mice. Notably, expression of IL-6 was selectively diminished in αCGRP−/− mice, suggesting that induction of IL-6 during acute inflammatory responses is blunted in αCGRP−/− mice. In addition, primary cultured αCGRP−/− hepatocytes were more susceptible to IFN-γ-induced cell death than hepatocytes from wild-type mice. Administration of exogenous αCGRP reduced the incidence of apoptosis among hepatocytes and endothelial cells. It thus appears that αCGRP exerts a hepatoprotective effect by modulating cytokine expression and preventing apoptosis.Biochemical and Biophysical Research Communications.
