title: Activation of tumor suppressor protein PTEN and induction of apoptosis are involved in cAMP-mediated inhibition of cell number in B92 glial cells.
abstract: During brain development, cAMP induces morphological changes and inhibits growth effects in several cell types. However, the molecular mechanisms underlying the growth inhibition remain unknown. Tumor suppressor protein phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase that inhibits the phosphoinositide 3-kinase (PI3K) pathway. The phosphorylation of Akt, which is one of the key molecules downstream of PI3K, inhibits apoptosis. In this study, we investigated the role of PTEN in cAMP-mediated growth inhibition. B92 rat glial cells were treated with 2 different cAMP stimulatory agents, a phosphodiesterase (PDE) inhibitor and a β-adrenoceptor agonist. Both cAMP stimulatory agents induced marked morphological changes in the cells, decreased cell number, decreased Akt phosphorylation, activated PTEN, cleaved caspase-3, and induced the condensation and fragmentation of nuclei. These results indicate that the cAMP stimulatory agents induced apoptosis. Protein phosphatase inhibitor prevented cAMP-induced dephosphorylation of PTEN and Akt. In addition, cAMP analogs and Epac-selective agonists affected PTEN and Akt activities. These results suggested that cAMP-induced apoptosis may be mediated by PTEN activation and Akt inhibition through protein phosphatase in B92 cells. Our results provide new insight into the role of PTEN in cAMP-induced apoptosis in glial cells.
authors.affiliation: Department of Physiology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Ishikawa, Kanazawa 920-8640, Japan. ns@med.kanazawa-u.ac.jp
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Sugimoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Miwa
authors.forename: Takako
authors.initials: T
authors.lastname: Ohno-Shosaku
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hitomi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Katsuro
authors.initials: K
authors.lastname: Tomita
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
authors.forename: Shoichi
authors.initials: S
authors.lastname: Koizumi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D009457:Neuroglia / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000242:Cyclic AMP; D051059:PTEN Phosphohydrolase