The induction of tuftelin expression in PC12 cell line during hypoxia and NGF-induced differentiation.

Abstract

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.

• Authors: Yoav Leiser, Nechama Silverstein, Anat Blumenfeld, Dekel Shilo, Amir Haze, Eli Rosenfeld, Boaz Shay, Rinat Tabakman, Shimon Lecht, Philip Lazarovici, Dan Deutsch
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 226 Issue 1 Pg. 165-72 (Jan 2011) ISSN: 1097-4652 [Electronic] United States
• PMID: 20658530 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dental Enamel Proteins
• Hif1a protein, rat
• Hypoxia-Inducible Factor 1, alpha Subunit
• RNA, Messenger
• RNA, Small Interfering
• tuftelin
• Cobalt
• Nerve Growth Factor
• Receptor, trkA
• cobaltous chloride
• Oxygen

Topics

• Adrenal Glands (drug effects, metabolism)
• Animals
• Cell Differentiation
• Cobalt (toxicity)
• Dental Enamel Proteins (genetics, metabolism)
• Gene Expression Regulation (drug effects)
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
• Mice
• Mice, Inbred BALB C
• Nerve Growth Factor (pharmacology)
• Oxygen (pharmacology)
• Oxygen Consumption (physiology)
• PC12 Cells
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering
• Rats
• Receptor, trkA (genetics, metabolism)
• Signal Transduction