TY - JOUR
T1 - Redox regulation of nerve growth factor-induced neuronal differentiation of PC12 cells through modulation of the nerve growth factor receptor, TrkA
AU - Kamata, Hideaki
AU - Oka, Shin Ichi
AU - Shibukawa, Yukinao
AU - Kakuta, Jungo
AU - Hirata, Hajime
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Encouragement of Young Scientists 08780746 from the Ministry of Education, Science, and Culture of Japan, and grants from the Tokyo Biochemical Research Foundation and the Brain Science Foundation.
PY - 2005/2/1
Y1 - 2005/2/1
N2 - We investigated the effects of the cellular redox state on nerve growth factor (NGF)-induced neuronal differentiation and its signaling pathways. Treatment of PC12 cells with buthionine sulfoximine (BSO) reduced the levels of GSH, a major cellular reductant, and enhanced NGF-induced neuronal differentiation, activation of AP-1 and the NGF receptor tyrosine kinase, TrkA. Conversely, incubation of the cells with a reductant, N-acetyl-l-cysteine (NAC), inhibited NGF-induced neuronal differentiation and AP-1 activation. Consistent with the suppression, NAC inhibited NGF-induced activation of TrkA, formation of receptor complexes comprising TrkA, Shc, Grb2, and Sos, and activation of phospholipase Cγ and phosphatidylinositol 3-kinase. Biochemical analysis suggested that the cellular redox state regulates TrkA activity through modulation of protein tyrosine phosphatases (PTPs). Thus, cellular redox state regulates signaling pathway of NGF through PTPs, and then modulates neuronal differentiation.
AB - We investigated the effects of the cellular redox state on nerve growth factor (NGF)-induced neuronal differentiation and its signaling pathways. Treatment of PC12 cells with buthionine sulfoximine (BSO) reduced the levels of GSH, a major cellular reductant, and enhanced NGF-induced neuronal differentiation, activation of AP-1 and the NGF receptor tyrosine kinase, TrkA. Conversely, incubation of the cells with a reductant, N-acetyl-l-cysteine (NAC), inhibited NGF-induced neuronal differentiation and AP-1 activation. Consistent with the suppression, NAC inhibited NGF-induced activation of TrkA, formation of receptor complexes comprising TrkA, Shc, Grb2, and Sos, and activation of phospholipase Cγ and phosphatidylinositol 3-kinase. Biochemical analysis suggested that the cellular redox state regulates TrkA activity through modulation of protein tyrosine phosphatases (PTPs). Thus, cellular redox state regulates signaling pathway of NGF through PTPs, and then modulates neuronal differentiation.
KW - N-Acetyl-l-cysteine
KW - NGF
KW - Neuronal differentiation
KW - PC12
KW - Protein tyrosine phosphatases
KW - Reactive oxygen species
KW - Redox
KW - TrkA
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U2 - 10.1016/j.abb.2004.07.036
DO - 10.1016/j.abb.2004.07.036
M3 - Article
C2 - 15629104
AN - SCOPUS:11144278530
SN - 0003-9861
VL - 434
SP - 16
EP - 25
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1 SPEC. ISS.
ER -