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The induction of tuftelin expression in PC12 cell line during hypoxia and NGF‐induced differentiation
Author(s) -
Leiser Yoav,
Silverstein Nechama,
Blumenfeld Anat,
Shilo Dekel,
Haze Amir,
Rosenfeld Eli,
Shay Boaz,
Tabakman Rinat,
Lecht Shimon,
Lazarovici Philip,
Deutsch Dan
Publication year - 2011
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.22318
Subject(s) - tropomyosin receptor kinase a , nerve growth factor , neurite , hypoxia (environmental) , biology , neurotrophin , cell culture , microbiology and biotechnology , endocrinology , medicine , receptor , chemistry , biochemistry , oxygen , genetics , organic chemistry , in vitro
The tuftelin protein isoforms undergo post‐translation modifications, and are ubiquitously expressed in various tissues in embryos, adults, and tumors. Developmental and pathological studies suggested an apparent correlation between oxygen deprivation and tuftelin expression. The aim of the study was therefore to investigate the effect of a pathological insult (hypoxia) and a physiological growth factor (NGF), which antagonistically regulate HIF1 expression, on tuftelin expression using the neuronal PC12 cell model. In the present study, we first demonstrated the expression of tuftelin in PC12 cells, providing an experimental system to investigate the pathophysiological role of tuftelin. Furthermore, we demonstrated the induction of tuftelin during hypoxia by oxygen deprivation and during chemical hypoxia by cobalt chloride. Down‐regulation of HIF1α mRNA blocked hypoxia‐induced HIF1α expression, and reduced by 89% hypoxia‐induced tuftelin expression. In mice, intraperitoneal injection of cobalt chloride significantly induced tuftelin mRNA and protein expression in the brain. During NGF‐mediated PC12 differentiation, tuftelin expression was significantly induced in correlation with neurite outgrowth. This induction was partially blocked by K252a, a selective antagonist of the NGF receptor TrkA, indicating the involvement of the TrkA‐signaling pathways in tuftelin induction by NGF. Revealing the physiological role of tuftelin will clarify mechanisms related to the “hypoxic genome,” and NGF‐induced neurotrophic and angiogenic effects. J. Cell. Physiol. 226: 165–172, 2010. © 2010 Wiley‐Liss, Inc.