Insulin-Like Growth Factor I (IGF-I) Protects Cells from Apoptosis by Alzheimer's V642I Mutant Amyloid Precursor Protein through IGF-I Receptor in an IGF-Binding Protein-Sensitive Manner

Niikura, Takako; Hashimoto, Yuichi; Okamoto, Takashi; Abe, Yoichiro; Yasukawa, Takashi; Kawasumi, Masaoki; Hiraki, Takako; Kita, Yoshiko; Terashita, Kenzo; Kouyama, Keisuke; Nishimoto, Ikuo

doi:10.1523/jneurosci.21-06-01902.2001

Cited by 70 publications

(59 citation statements)

References 73 publications

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“…pHN mutants were constructed by a site-directed mutagenesis kit (Stratagene). Catalytically negative (CN-) procaspase-3 cDNA was described (13). Antibodies against PS N termini were provided by T. Tomita and T. Iwatsubo (University of Tokyo).…”

Section: Methodsmentioning

confidence: 99%

A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ

Hashimoto

Niikura

Tajima

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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548

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There is no proof that the HN cDNA represents a gene, that its origin is nuclear, or that the HN peptide is produced in vivo. The information that the long HN cDNA sequence is virtually identical to mitochondrial rRNA should have been put in the Discussion rather than published as supplementary material. The Discussion should have contained the following:The long cDNA [1,567 bp including a poly(A) tail] containing the HN ORF is Ͼ99% identical (1548͞1552) to positions 1679-3230 of mitochondrial DNA (GenBank accession no. AB055387). Because mitochondrial DNA positions 1667-3224 code for mitochondrial 16S rRNA, and mitochondrial 16S rRNA has a short poly(A) tail during transcription (1), the virtual identity of the long HN cDNA to mitochondrial DNA indicates that HN cDNA is mitochondrial 16S rRNA with a poly(A) tail. This makes it unlikely that the peptide encoded by the ORF in HN cDNA is naturally produced. Further, the 75-bp HN ORF is separated from the 5Ј end of the long HN cDNA by a 950-bp region containing at least seven ORFs, each with a stop codon. This makes it even more unlikely that HN peptide is produced from the long HN cDNA. It should also be noted that mitochondria-like nuclear sequences occur commonly as pseudogenes (2). Finally, the HN peptide lacks the characteristic N-terminal signal sequence of secreted peptides, although we suggest that a signal peptide-like function may be encoded in the primary sequence of HN peptide. For all of these reasons, it is unlikely that the HN ORF leads to production of the predicted peptide in vivo.Nonetheless, it remains possible that HN cDNA represents a nuclear transcribed mRNA and that the HN peptide is a natural product. Long regions of the HN cDNA are Ͼ99% identical to certain registered human mRNAs [1545͞1553 at positions 14-1580 of FLJ22981 fis cDNA (AK026634), 925͞929 at positions 1-929 of FLJ22517 fis cDNA, 914͞919 at positions 1348-2266 of FLJ20341 fis cDNA, and 345͞346 at positions 1-346 of PNAS-32 mRNA]. PNAS-32 mRNA is actually expressed to produce NB4 apoptosis-related protein, showing that this mRNA is transcribed from a nuclear gene. In addition, HN cDNA is highly similar to regions of more than 1,000 bp on human chromosomes [positions 245364-244075 of chromosome 11 draft sequence (92%, 1198͞1290), positions 65752-66775 of chromosome X draft sequence (95%, 974͞1025), and positions 687598-688608 of chromosome 5 draft sequence (93%, 954͞1016)]. Also, the HN ORF has a Kozak-like sequence, although it is not canonical.

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Section: Methodsmentioning

confidence: 99%

A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ

Hashimoto

Niikura

Tajima

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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548

664

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“…F11 cells, the hybrid cells of a rat embryonic day 13 (E13) primary cultured neuron and a mouse neuroblastoma, were grown in Ham's F-12 (Life Technologies, Gaithersburg, MD) plus 18% fetal bovine serum (FBS) (Hyclone, L ogan, UT) and antibiotics, as described previously (Platika et al, 1985;Yamatsuji et al, 1996;Huang et al, 2000;Niikura et al, 2001). F11 cells (7 ϫ 10 4 cells per well in a six-well plate cultured in Ham's F-12 plus 18% FBS for 12-16 hr) were transfected with plasmids encoding FAD genes by lipofection [1 g of FAD cDNA, 2 l of LipofectAM I N E, and 4 l of PLUS reagent (Life Technologies)] in the absence of serum for 3 hr and were incubated with Ham's F-12 plus 18% FBS for 2 hr.…”

Section: Methodsmentioning

confidence: 99%

Detailed Characterization of Neuroprotection by a Rescue Factor Humanin against Various Alzheimer's Disease-Relevant Insults

et al. 2001

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A novel factor, termed Humanin (HN), antagonizes against neurotoxicity by various types of familial Alzheimer's disease (AD) genes [V642I and K595N/M596L (NL) mutants of amyloid precursor protein (APP), M146L-presenilin (PS) 1, and N141I-PS2] and by A␤1-43 with clear action specificity ineffective on neurotoxicity by polyglutamine repeat Q79 or superoxide dismutase 1 mutants. Here we report that HN can also inhibit neurotoxicity by other AD-relevant insults: other familial AD genes (A617G-APP, L648P-APP, A246E-PS1, L286V-PS1, C410Y-PS1, and H163R-PS1), APP stimulation by anti-APP antibody, and other A␤ peptides (A␤1-42 and A␤25-35). The action specificity was further indicated by the finding that HN could not suppress neurotoxicity by glutamate or prion fragment. Against the AD-relevant insults, essential roles of Cys 8 and Ser 14 were commonly indicated, and the domain from Pro 3 to Pro 19 was responsible for the rescue action of HN, in which seven residues turned out to be essential. We also compared the neuroprotective action of S14G HN (HNG) with that of activity-dependent neurotrophic factor, IGF-I, or basic FGF for the antagonism against various AD-relevant insults (V642I-APP, NL-APP, M146L-PS1, N141I-PS2, and A␤1-43). Although all of these factors could abolish neurotoxicity by A␤1-43, only HNG could abolish cytotoxicities by all of them. HN and HN derivative peptides may provide a new insight into the study of AD pathophysiology and allow new avenues for the development of therapeutic interventions for various forms of AD.

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“…IGF-I may be a key factor in regulating the clearance of A␤ from the brain through carrier-mediated transport (4). Furthermore, IGF-I has been shown to protect against several neurodegenerative conditions both in vitro and in vivo, including A␤-induced cell death (5).…”

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confidence: 99%

Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis

Ikonen

Liu²,

Hashimoto³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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253

240

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Insulin-Like Growth Factor I (IGF-I) Protects Cells from Apoptosis by Alzheimer's V642I Mutant Amyloid Precursor Protein through IGF-I Receptor in an IGF-Binding Protein-Sensitive Manner

Cited by 70 publications

References 73 publications

A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ

A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ

Detailed Characterization of Neuroprotection by a Rescue Factor Humanin against Various Alzheimer's Disease-Relevant Insults

Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis

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