2. Academic Validation
  3. N-Formylated humanin activates both formyl peptide receptor-like 1 and 2

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

  • Biochem Biophys Res Commun. 2004 Nov 5;324(1):255-61. doi: 10.1016/j.bbrc.2004.09.046.
Masataka Harada 1,  Yugo Habata,  Masaki Hosoya,  Kazunori Nishi,  Ryo Fujii,  Makoto Kobayashi,  Shuji Hinuma
Affiliations

Affiliation

  • 1 Discovery Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan. [email protected]
PMID: 15465011 DOI: 10.1016/j.bbrc.2004.09.046
Abstract

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 (EC(50)) value of HN was 3.5nM, while that of fHN was 0.012nM. We demonstrated by binding experiments using [(125)I]-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.

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