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Singlet Oxygen–induced Activation of Akt/Protein Kinase B is Independent of Growth Factor Receptors ¶
Author(s) -
Zhuang Shougang,
Kochevar Irene E.
Publication year - 2003
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2003)0780361soaopk2.0.co2
Subject(s) - protein kinase b , microbiology and biotechnology , phosphorylation , pi3k/akt/mtor pathway , signal transduction , platelet derived growth factor receptor , chemistry , tyrosine phosphorylation , cancer research , growth factor receptor , receptor tyrosine kinase , biology , growth factor , biochemistry , receptor
Singlet oxygen ( 1 O 2 )–induced cytotoxicity is believed to be responsible for responses to photodynamic therapy and for apoptosis of T helper cells after UV‐A treatment. Other cytotoxic oxidants, such as hydrogen peroxide and peroxynitrite have been shown to stimulate cell survival signaling pathways in addition to causing cell death. Both these oxidants stimulate the Akt/protein kinase B survival signaling pathway through activation of membrane tyrosine kinase growth factor receptors. We evaluated the ability of 1 O 2 to activate the Akt/protein kinase B pathway in NIH 3T3 cells and examined potential activation pathways. Exposure of fibroblasts to 1 O 2 elicited a strong and sustained phosphorylation of Akt, which occurred concurrently with phosphorylation of p38 kinase, a proapoptotic signal. Inhibition of phosphatidylinositol‐3‐OH kinase (PI3‐K) completely blocked Akt phosphorylation. Significantly, cell death induced by 1 O 2 was enhanced by inhibition of PI3‐K, suggesting that activation of Akt by 1 O 2 may contribute to fibroblast survival under this form of oxidative stress. 1 O 2 treatment did not induce phosphorylation of platelet‐derived growth factor receptor (PDGFR) or activate SH‐PTP2, a substrate of growth factor receptors, suggesting that PDGFR was not activated. In addition, specific inhibition of PDGFR did not affect Akt phosphorylation elicited by 1 O 2 . Activation of neither focal adhesion kinase (FAK) nor Ras protein, both of which mediate responses to reactive oxygen species, appeared to be pathways for the 1 O 2 ‐induced activation of the PI3‐K–Akt survival pathway. Thus, activation of Akt by 1 O 2 is mediated by PI3‐K and contributes to a survival response that counteracts cell death after 1 O 2 ‐induced injury. However, unlike the response to other oxidants, activation of the PI3‐K–Akt by 1 O 2 does not involve activation of growth factor receptors, FAK or Ras protein.