Evidence for in vivo production of Humanin peptide, a neuroprotective factor against Alzheimer's disease-related insults.
An unbiased functional screening with brain cDNA library from an Alzheimer's disease (AD) brain identified a novel 24-residue peptide Humanin (HN), which suppresses AD-related neurotoxicity. As the 1567-base cDNA containing the open reading frame (ORF) of HN is 99% identical to mitochondrial 16S ribosomal RNA as well as registered human mRNA, it was elusive whether HN is produced in vivo. Here, we raised anti-HN antibody and found that long cDNAs containing the ORF of HN (HN-ORF) produced the HN peptide in mammalian cells, dependent on the presence of full-length HN-ORF. Immunoblot analysis detected a 3-kDa protein with HN immunoreactivity in the testis and the colon in 3-week-old mice and in the testis in 12-week-old mice. HN immunoreactivity was also detected in an AD brain, but little in normal brains. This study suggests that HN peptide could be produced in vivo, and would provide a novel insight into the pathophysiology of AD.
Tajima
Hirohisa
H
Department of Pharmacology and Neurosciences, KEIO University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Niikura
Takako
T
Hashimoto
Yuichi
Y
Ito
Yuko
Y
Kita
Yoshiko
Y
Terashita
Kenzo
K
Yamazaki
Kazuto
K
Koto
Atsuo
A
Aiso
Sadakazu
S
Nishimoto
Ikuo
I
D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003106:Colon / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism*; D016366:Open Reading Frames / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000235:genetics; D013737:Testis / Q000378:metabolism
D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D011506:Proteins; D012335:RNA, Ribosomal; C427211:humanin