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Resistance to TGF‐β‐induced apoptosis in regenerating hepatocytes
Author(s) -
Herrera Blanca,
Álvarez Alberto M.,
Beltrán Jesús,
Valdés Francisco,
Fabregat Isabel,
Fernández Margarita
Publication year - 2004
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20078
Subject(s) - apoptosis , transforming growth factor , microbiology and biotechnology , resistance (ecology) , chemistry , biology , genetics , ecology
Treatment with transforming growth factor beta (TGF‐β) of hepatocytes from two different proliferative conditions, such as fetal development and adult liver regeneration, shows that regenerating cells respond to this cytokine in terms of growth inhibition, but are less sensitive than the fetal ones to the apoptosis induced by this factor. Regenerating TGF‐β treated cells show higher cell viability and lower percentage of apoptotic cells than the fetal treated ones. Furthermore, TGF‐β treated regenerating hepatocytes maintain a well‐preserved parenchyma‐like organization. Treatment with TGF‐β induces the loss of mitochondrial transmembrane potential in fetal but not in regenerating hepatocytes and activation of caspase‐3 is lower in regenerating than in fetal cells. Regenerating hepatocytes show higher intracellular levels of some antiapoptotic proteins, such as Bcl‐x L and c‐IAP‐1 and, interestingly, they present higher intracellular glutathione levels, which might provide of mechanisms to avoid potential dangerous effects of the oxidative stress‐mediated apoptosis induced by TGF‐β. In fact, treatment with BSO (a glutathione synthesis inhibitor) restores the response of regenerating hepatocytes to TGF‐β in terms of cell death. In conclusion, increased levels of Bcl‐x L and cIAP‐1 and higher intracellular glutathione levels could confer resistance to the apoptosis induced by TGF‐β during liver regeneration. © 2004 Wiley‐Liss, Inc.