Cobalt chloride induces neurite outgrowth in rat pheochromocytoma PC-12 cells through regulation of endothelin-2/vasoactive intestinal contractor.

Abstract

We investigated whether endothelin-2/vasoactive intestinal contractor (ET-2/VIC) gene expression, upregulated by hypoxia in cancer cells, was associated with differentiation in neuronal cells. RT-PCR analysis, morphological observations, and immunostaining revealed that CoCl2, a hypoxic mimetic agent, at 200 microM increased expression of the ET-2/VIC gene, decreased expression of the ET-1 gene, and induced neurite outgrowth in PC-12 rat pheochromocytoma cells. These effects induced by 200 microM CoCl2 were completely inhibited by the antioxidant N-acetyl cysteine at 20 mM. In addition, CoCl2 increased the level of intracellular reactive oxygen species (ROS) at an early stage. Furthermore, interleukin (IL)-6 gene expression was upregulated upon the differentiation induced by CoCl2. These results suggest that expression of ET-2/VIC and ET-1 mediated by ROS may be associated with neuronal differentiation through the regulation of IL-6. When the cells were treated with 500 microM CoCl2 for 24 hr, however, ET-2/VIC gene expression disappeared, IL-6 gene expression was downregulated, and necrosis was subsequently induced in the PC-12 cells.

• Authors: Eiichi Kotake-Nara, Satoshi Takizawa, Jiexia Quan, Hongyu Wang, Kaname Saida
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 81 Issue 4 Pg. 563-71 (Aug 15 2005) ISSN: 0360-4012 [Print] United States
• PMID: 15948191 (Publication Type: Journal Article)
• Copyright: 2005 Wiley-Liss, Inc.

Chemical References

• Antimutagenic Agents
• Antioxidants
• Endothelin-1
• Endothelin-2
• Intercellular Signaling Peptides and Proteins
• Interleukin-6
• Peptides
• Reactive Oxygen Species
• vasoactive intestinal constrictor
• Cobalt
• cobaltous chloride

Topics

• Animals
• Antimutagenic Agents (pharmacology)
• Antioxidants (pharmacology)
• Cell Differentiation (drug effects, physiology)
• Cell Division (drug effects, physiology)
• Cobalt (pharmacology)
• Endothelin-1 (genetics, metabolism)
• Endothelin-2 (genetics, metabolism)
• Gene Expression (drug effects, physiology)
• Intercellular Signaling Peptides and Proteins
• Interleukin-6 (genetics)
• Neurites (drug effects, physiology)
• PC12 Cells
• Peptides (genetics, metabolism)
• Rats
• Reactive Oxygen Species (metabolism)