A novel rat gene encoding a Humanin-like peptide endowed with broad neuroprotective activity.

Andrea Caricasole, Valeria Bruno, Irene Cappuccio, Daniela Melchiorri, Agata Copani, Ferdinando Nicoletti

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

We report the identification of a novel rat cDNA encoding a peptide homologous to Humanin, a secreted peptide that specifically protects against neuronal cell death induced by beta-amyloid peptide (Ab) or by mutations causing early-onset familial Alzheimer's disease. The rat gene, which we termed Rattin, encodes a peptide of 38 residues (15 residues longer than Humanin) showing 73% identity in the conserved region to Humanin. The expression profile of the 1.6-kb Rattin transcript is comparable to that displayed by Humanin, with significant expression levels in the central nervous system and in cardiac and skeletal muscle. The full-length Rattin peptide and its 1-25 fragment were equally effective as Humanin in protecting rat- and mouse-cultured cortical neurons against Ab-induced toxicity. However, Rattin was much more effective than Humanin against excitotoxic neuronal death induced by a toxic pulse with NMDA. Rattin and its short fragment were protective against excitotoxic death not only when coapplied with NMDA, but also when added to the cultures after the NMDA pulse. Neither Rattin not Humanin could affect neuronal apoptosis by trophic deprivation induced in cultured cerebellar granule cells depleted of extracellular potassium. This suggests that Rattin is the prototype of a novel class of peptides, phylogenetically related to Humanin, endowed with protective activity not only against Ab but also toward excitotoxic neuronal death. The identification of Rattin may be instrumental for the development of novel pharmacological strategies aimed at enhancing the production of endogenous Humanin-like peptides.

Original languageEnglish
Pages (from-to)1331-1333
Number of pages3
JournalFASEB Journal
Volume16
Issue number10
Publication statusPublished - 2002

Fingerprint

Gene encoding
Rats
Peptides
Genes
N-Methylaspartate
Alzheimer Disease
humanin
Poisons
Amyloid beta-Peptides
Neurology
Cell death
Neurons
Toxicity
Muscle
Myocardium
Potassium
Skeletal Muscle
Cell Death
Central Nervous System
Complementary DNA

Cite this

A novel rat gene encoding a Humanin-like peptide endowed with broad neuroprotective activity. / Caricasole, Andrea; Bruno, Valeria; Cappuccio, Irene; Melchiorri, Daniela; Copani, Agata; Nicoletti, Ferdinando.

In: FASEB Journal, Vol. 16, No. 10, 2002, p. 1331-1333.

Research output: Contribution to journalArticle

Caricasole, A, Bruno, V, Cappuccio, I, Melchiorri, D, Copani, A & Nicoletti, F 2002, 'A novel rat gene encoding a Humanin-like peptide endowed with broad neuroprotective activity.', FASEB Journal, vol. 16, no. 10, pp. 1331-1333.
Caricasole, Andrea ; Bruno, Valeria ; Cappuccio, Irene ; Melchiorri, Daniela ; Copani, Agata ; Nicoletti, Ferdinando. / A novel rat gene encoding a Humanin-like peptide endowed with broad neuroprotective activity. In: FASEB Journal. 2002 ; Vol. 16, No. 10. pp. 1331-1333.
@article{ff2c65e8a87b4e67babdfbe95ded248d,
title = "A novel rat gene encoding a Humanin-like peptide endowed with broad neuroprotective activity.",
abstract = "We report the identification of a novel rat cDNA encoding a peptide homologous to Humanin, a secreted peptide that specifically protects against neuronal cell death induced by beta-amyloid peptide (Ab) or by mutations causing early-onset familial Alzheimer's disease. The rat gene, which we termed Rattin, encodes a peptide of 38 residues (15 residues longer than Humanin) showing 73{\%} identity in the conserved region to Humanin. The expression profile of the 1.6-kb Rattin transcript is comparable to that displayed by Humanin, with significant expression levels in the central nervous system and in cardiac and skeletal muscle. The full-length Rattin peptide and its 1-25 fragment were equally effective as Humanin in protecting rat- and mouse-cultured cortical neurons against Ab-induced toxicity. However, Rattin was much more effective than Humanin against excitotoxic neuronal death induced by a toxic pulse with NMDA. Rattin and its short fragment were protective against excitotoxic death not only when coapplied with NMDA, but also when added to the cultures after the NMDA pulse. Neither Rattin not Humanin could affect neuronal apoptosis by trophic deprivation induced in cultured cerebellar granule cells depleted of extracellular potassium. This suggests that Rattin is the prototype of a novel class of peptides, phylogenetically related to Humanin, endowed with protective activity not only against Ab but also toward excitotoxic neuronal death. The identification of Rattin may be instrumental for the development of novel pharmacological strategies aimed at enhancing the production of endogenous Humanin-like peptides.",
author = "Andrea Caricasole and Valeria Bruno and Irene Cappuccio and Daniela Melchiorri and Agata Copani and Ferdinando Nicoletti",
year = "2002",
language = "English",
volume = "16",
pages = "1331--1333",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "10",

}

TY - JOUR

T1 - A novel rat gene encoding a Humanin-like peptide endowed with broad neuroprotective activity.

AU - Caricasole, Andrea

AU - Bruno, Valeria

AU - Cappuccio, Irene

AU - Melchiorri, Daniela

AU - Copani, Agata

AU - Nicoletti, Ferdinando

PY - 2002

Y1 - 2002

N2 - We report the identification of a novel rat cDNA encoding a peptide homologous to Humanin, a secreted peptide that specifically protects against neuronal cell death induced by beta-amyloid peptide (Ab) or by mutations causing early-onset familial Alzheimer's disease. The rat gene, which we termed Rattin, encodes a peptide of 38 residues (15 residues longer than Humanin) showing 73% identity in the conserved region to Humanin. The expression profile of the 1.6-kb Rattin transcript is comparable to that displayed by Humanin, with significant expression levels in the central nervous system and in cardiac and skeletal muscle. The full-length Rattin peptide and its 1-25 fragment were equally effective as Humanin in protecting rat- and mouse-cultured cortical neurons against Ab-induced toxicity. However, Rattin was much more effective than Humanin against excitotoxic neuronal death induced by a toxic pulse with NMDA. Rattin and its short fragment were protective against excitotoxic death not only when coapplied with NMDA, but also when added to the cultures after the NMDA pulse. Neither Rattin not Humanin could affect neuronal apoptosis by trophic deprivation induced in cultured cerebellar granule cells depleted of extracellular potassium. This suggests that Rattin is the prototype of a novel class of peptides, phylogenetically related to Humanin, endowed with protective activity not only against Ab but also toward excitotoxic neuronal death. The identification of Rattin may be instrumental for the development of novel pharmacological strategies aimed at enhancing the production of endogenous Humanin-like peptides.

AB - We report the identification of a novel rat cDNA encoding a peptide homologous to Humanin, a secreted peptide that specifically protects against neuronal cell death induced by beta-amyloid peptide (Ab) or by mutations causing early-onset familial Alzheimer's disease. The rat gene, which we termed Rattin, encodes a peptide of 38 residues (15 residues longer than Humanin) showing 73% identity in the conserved region to Humanin. The expression profile of the 1.6-kb Rattin transcript is comparable to that displayed by Humanin, with significant expression levels in the central nervous system and in cardiac and skeletal muscle. The full-length Rattin peptide and its 1-25 fragment were equally effective as Humanin in protecting rat- and mouse-cultured cortical neurons against Ab-induced toxicity. However, Rattin was much more effective than Humanin against excitotoxic neuronal death induced by a toxic pulse with NMDA. Rattin and its short fragment were protective against excitotoxic death not only when coapplied with NMDA, but also when added to the cultures after the NMDA pulse. Neither Rattin not Humanin could affect neuronal apoptosis by trophic deprivation induced in cultured cerebellar granule cells depleted of extracellular potassium. This suggests that Rattin is the prototype of a novel class of peptides, phylogenetically related to Humanin, endowed with protective activity not only against Ab but also toward excitotoxic neuronal death. The identification of Rattin may be instrumental for the development of novel pharmacological strategies aimed at enhancing the production of endogenous Humanin-like peptides.

UR - http://www.scopus.com/inward/record.url?scp=0036673025&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036673025&partnerID=8YFLogxK

M3 - Article

C2 - 12154011

AN - SCOPUS:0036673025

VL - 16

SP - 1331

EP - 1333

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 10

ER -