N-formylated humanin activates both formyl peptide receptor-like 1 and 2

被引：105

作者：

Harada, M ^{[1
]}

Habata, Y ^{[1
]}

Hosoya, M ^{[1
]}

Nishi, K ^{[1
]}

Fujii, R ^{[1
]}

Kobayashi, M ^{[1
]}

Hinuma, S ^{[1
]}

机构：

[1] Takeda Pharmaceut Co Ltd, Div Pharmaceut Res, Discovery Res Labs, Tsukuba, Ibaraki 3004293, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 324卷 / 01期

关键词：

formyl peptide receptor-like 1; formyl peptide receptor-like 2; humanin; mitochondria; chemotaxis; Alzheimer's disease;

D O I：

10.1016/j.bbrc.2004.09.046

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have discovered that humanin (HN) acts as a ligand for formyl peptide receptor-like 1 (FPRL1) and 2 (FPRL2). This discovery was based on our finding that HN suppressed forskolin-induced cAMP production in Chinese hamster ovary (CHO) cells expressing human FPRL1 (CHO-hFPRL1) or human FPRL2 (CHO-hFPRL2). In addition, we found that N-formylated HN (fHN) performed more potently as a ligand for FPRL1 than HN: in CHO-hFPRL1 cells, the effective concentration for the half-maximal response (EC50) value of HN was 3.5 nM, while that of fHN was 0.012 nM. We demonstrated by binding experiments using [I-125]-W peptide that HN and fHN directly interacted with hFPRL1 on the membrane. In addition, we found that HN and fHN showed strong chemotactic activity for CHO-hFPRL1 and CHO-hFPRL2 cells. HN is known to have a protective effect against neuronal cell death. Our findings contribute to the understanding of the mechanism behind HN's function. (C) 2004 Elsevier Inc. All rights reserved.

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页码：255 / 261

页数：7

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