Prion Protein and Its Ligand Stress Inducible Protein 1 Regulate Astrocyte Development

Author(s)

Arantes, Camila ^{[1, 2]} ; Nomiz, Regina ^[3] ; Lopes, Marilene H. ^[2] ; Hajj, Glaucia N. M. ^[2] ; Lima, Flavia R. S. ^[2] ; Martins, Vilma R. ^[2]

Affiliation

^[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-01498 Sao Paulo - Brazil

^[2] Hosp Alemao Oswaldo Cruz, Ludwig Inst Canc Res, Sao Paulo - Brazil

^[3] Hosp AC Camargo Fund Antonio Prudente, Ctr Tratamento & Pesquisa, Sao Paulo - Brazil

• Document type: Journal article
• Source: Glia; v. 57, n. 13, p. 1439-1449, OCT 2009.
• Web of Science Citations: 38

Abstract

Prion protein (PrP(C)) interaction with stress inducible protein 1 (STI1) mediates neuronal survival and differentiation. However, the function of PrP(C) in astrocytes has not been approached. In this study, we show that STI1 prevents cell death in wild-type astrocytes in a protein kinase A-dependent manner, whereas PrP(C)-null astrocytes were not affected by STI1 treatment. At embryonic day 17, cultured astrocytes and brain extracts derived from PrP(C)-null mice showed a reduced expression of glial fibrillary acidic protein (GFAP) and increased vimentin and nestin expression when compared with wild-type, suggesting a slower rate of astrocyte maturation in PrP(C)-null animals. Furthermore, PrP(C)-null astrocytes treated with STI1 did not differentiate from a flat to a process-bearing morphology, as did wild-type astrocytes. Remarkably, STI1 inhibited proliferation of both wild-type and PrP(C)-null astrocytes in a protein kinase C-dependent manner. Taken together, our data show that PrP(C) and STI1 are essential to astrocyte development and act through distinct signaling pathways.(C) 2009 Wiley-Liss, Inc. (AU)

• FAPESP's process: 03/13189-2 - The role of celular prion protein in physiological and pathological processes II
• Grantee: Vilma Regina Martins
• Support Opportunities: Research Projects - Thematic Grants