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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Effects and Mechanism of Organ Protection by Cardiotrophin-1

Author(s): MªB. Garcia-Cenador, J.M. Lopez-Novoa, J. Diez and F.J. Garcia-Criado

Volume 20 , Issue 2 , 2013

Page: [246 - 256] Pages: 11

DOI: 10.2174/0929867311320020005

Price: $65

Abstract

Cardiotrophin-1 (CT-1), a member of the interleukin (IL)-6 family, is reported to exhibit a plethora of pleiotropic effects in the heart such as cytoprotective, pro-proliferative and pro-fibrotic ones. An extensive research has been devoted on proliferative and profibrotic effects of CT-1on the heart. Thus the present review has been aimed to critically define the cytoprotective effects of CT-1 and the cellular and molecular mechanisms involved in them. Although many effects of CT-1 have been described on the heart, CT-1has now also been reported to exhibit important protective effects in other organs such as liver, kidney or nervous system. CT-1 produces its effects through a unique receptor system comprising LIF receptor (LIFRβ) and a common signal transducer, the glycoprotein 130 (gp130). The signaling pathway downstream from gp130 is based on at least, three distinct pathways: 1) the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, 2) the p42/44 mitogen-activated protein kinase (p42/44 MAPK) pathway, also known as the extracellular receptor kinase-1/2 (ERK1/2) pathway, and 3) the phosphatidylinositol 3-OH kinase (PI3K)/Akt pathway. Since CT-1 easily achieves its cytoprotective effects via a combination of the above three signaling pathways, it becomes quite necessary to determine which pathway(s) is involved in each particular effect of CT-1. In each of its target organs, CT-1 may also display differential mechanisms of cytoprotection, and thus it is relevant to understand how these mechanisms are locally regulated.

Keywords: Cardiotrophin-1, cytokines, cytoprotection, heart, gp130, IL-6, JAK, LIF receptor, liver, SOCS, STAT


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