TY - JOUR
T1 - Involvement of tyrosine kinases and STAT3 in Humanin-mediated neuroprotection
AU - Hashimoto, Yuichi
AU - Suzuki, Hiroaki
AU - Aiso, Sadakazu
AU - Niikura, Takako
AU - Nishimoto, Ikuo
AU - Matsuoka, Masaaki
N1 - Funding Information:
This work was supported in part by a grant from the Takeda Medical Research Foundation (Y.H.), and the Japan Society for the Promotion of Science.
PY - 2005/10/28
Y1 - 2005/10/28
N2 - Humanin (HN) inhibits neuronal cell death induced by various Alzheimer's disease (AD)-related insults. It has been proposed that HN binds to a putative receptor on the cell membrane and triggers a signal transduction cascade linked to neuroprotection. Recently, it was shown that HN binds to pertussis toxin (PTX)-sensitive G protein-coupled formylpeptide receptor-like-1 molecule (FPRL-1), reduces Aβ(1-42) aggregation and fibril formation, and suppresses the Aβ(1-42) toxicity on mononuclear phagocytic cells [Ying, G., Iribarren, P., Zhou, Y., Gong, W., Zhang, N., Yu, Z.X., Le, Y., Cui, Y., Wang, J.M., 2004. Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. Journal of Immunology 172 (11), 7078-7085.]. We here show that siRNA-mediated disruption of expression of the mouse counterpart of FPRL-1, FPR2, did not result in attenuation of HN-mediated rescue of neuronal cell death induced by AD-related insults. We simultaneously provide evidence that neuroprotection by HN in F11 cells is mediated by the STAT3 transcription factor as well as by certain tyrosine kinases. Altogether, we speculate that a receptor other than FPR2 exists that mediates HN neuroprotection in F11 neurohybrid cells
AB - Humanin (HN) inhibits neuronal cell death induced by various Alzheimer's disease (AD)-related insults. It has been proposed that HN binds to a putative receptor on the cell membrane and triggers a signal transduction cascade linked to neuroprotection. Recently, it was shown that HN binds to pertussis toxin (PTX)-sensitive G protein-coupled formylpeptide receptor-like-1 molecule (FPRL-1), reduces Aβ(1-42) aggregation and fibril formation, and suppresses the Aβ(1-42) toxicity on mononuclear phagocytic cells [Ying, G., Iribarren, P., Zhou, Y., Gong, W., Zhang, N., Yu, Z.X., Le, Y., Cui, Y., Wang, J.M., 2004. Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. Journal of Immunology 172 (11), 7078-7085.]. We here show that siRNA-mediated disruption of expression of the mouse counterpart of FPRL-1, FPR2, did not result in attenuation of HN-mediated rescue of neuronal cell death induced by AD-related insults. We simultaneously provide evidence that neuroprotection by HN in F11 cells is mediated by the STAT3 transcription factor as well as by certain tyrosine kinases. Altogether, we speculate that a receptor other than FPR2 exists that mediates HN neuroprotection in F11 neurohybrid cells
KW - Alzheimer's disease
KW - FPR2
KW - FPRL-1
KW - Humanin
KW - Neuronal cell death
KW - STAT3
KW - Tyrosine kinase
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U2 - 10.1016/j.lfs.2005.03.031
DO - 10.1016/j.lfs.2005.03.031
M3 - Article
C2 - 16005025
AN - SCOPUS:26444463390
SN - 0024-3205
VL - 77
SP - 3092
EP - 3104
JO - Life Sciences
JF - Life Sciences
IS - 24
ER -