ProNGF processing in adult rat tissues and bioactivity of NGF prodomain peptides

The neurotrophin nerve growth factor (NGF) and its precursor proNGF are both bioactive and exert similar or opposite actions depending on the cell target and its milieu. The balance between NGF and proNGF is crucial for cell and tissue homeostasis and it is considered an indicator of pathological co...

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Main Authors: Marie Anne Makoudjou, Elena Fico, Pamela Rosso, Viviana Triaca, Lucio De Simone, Daniela Rossetti, Franca Cattani, Marcello Allegretti, Paola Tirassa
Format: Article
Language:English
Published: Wiley 2024-04-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.13768
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author Marie Anne Makoudjou
Elena Fico
Pamela Rosso
Viviana Triaca
Lucio De Simone
Daniela Rossetti
Franca Cattani
Marcello Allegretti
Paola Tirassa
author_facet Marie Anne Makoudjou
Elena Fico
Pamela Rosso
Viviana Triaca
Lucio De Simone
Daniela Rossetti
Franca Cattani
Marcello Allegretti
Paola Tirassa
author_sort Marie Anne Makoudjou
collection DOAJ
description The neurotrophin nerve growth factor (NGF) and its precursor proNGF are both bioactive and exert similar or opposite actions depending on the cell target and its milieu. The balance between NGF and proNGF is crucial for cell and tissue homeostasis and it is considered an indicator of pathological conditions. Proteolytical cleavage of proNGF to the mature form results in different fragments, whose function and/or bioactivity is still unclear. The present study was conducted to investigate the distribution of proNGF fragments derived from endogenous cleavage in brain and peripheral tissues of adult rats in the healthy condition and following inflammatory lipopolysaccharide (LPS) challenge. Different anti‐proNGF antibodies were tested and the presence of short peptides corresponding to the prodomain sequence (pdNGFpep) was identified. Processing of proNGF was found to be tissue‐specific and accumulation of pdNGFpeps was found in inflamed tissues, mainly in testis, intestine and heart, suggesting a possible correlation between organ functions and a response to insults and/or injury. The bioactivity of pdNGFpep was also demonstrated in vitro by using primary hippocampal neurons. Our study supports a biological function for the NGF precursor prodomain and indicates that short peptides from residues 1–60, differing from the 70–110 sequence, induce apoptosis, thereby opening the way for identification of new molecular targets to study pathological conditions.
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spelling doaj.art-b0ab1350e18643218da57bfbfb5c37082024-04-03T10:12:36ZengWileyFEBS Open Bio2211-54632024-04-0114464365410.1002/2211-5463.13768ProNGF processing in adult rat tissues and bioactivity of NGF prodomain peptidesMarie Anne Makoudjou0Elena Fico1Pamela Rosso2Viviana Triaca3Lucio De Simone4Daniela Rossetti5Franca Cattani6Marcello Allegretti7Paola Tirassa8Cellular and Molecular Biology, Department of Biology University of Rome “Tor Vergata” Rome ItalyInstitute of Biochemistry and Cell Biology (IBBC) National Research Council (CNR) Rome ItalyInstitute of Biochemistry and Cell Biology (IBBC) National Research Council (CNR) Rome ItalyInstitute of Biochemistry and Cell Biology (IBBC) National Research Council (CNR) Campus A. Buzzati‐Traverso, Monterotondo Rome ItalyDompé Farmaceutici S.p.A L'Aquila ItalyDompé Farmaceutici S.p.A L'Aquila ItalyDompé Farmaceutici S.p.A L'Aquila ItalyDompé Farmaceutici S.p.A L'Aquila ItalyInstitute of Biochemistry and Cell Biology (IBBC) National Research Council (CNR) Rome ItalyThe neurotrophin nerve growth factor (NGF) and its precursor proNGF are both bioactive and exert similar or opposite actions depending on the cell target and its milieu. The balance between NGF and proNGF is crucial for cell and tissue homeostasis and it is considered an indicator of pathological conditions. Proteolytical cleavage of proNGF to the mature form results in different fragments, whose function and/or bioactivity is still unclear. The present study was conducted to investigate the distribution of proNGF fragments derived from endogenous cleavage in brain and peripheral tissues of adult rats in the healthy condition and following inflammatory lipopolysaccharide (LPS) challenge. Different anti‐proNGF antibodies were tested and the presence of short peptides corresponding to the prodomain sequence (pdNGFpep) was identified. Processing of proNGF was found to be tissue‐specific and accumulation of pdNGFpeps was found in inflamed tissues, mainly in testis, intestine and heart, suggesting a possible correlation between organ functions and a response to insults and/or injury. The bioactivity of pdNGFpep was also demonstrated in vitro by using primary hippocampal neurons. Our study supports a biological function for the NGF precursor prodomain and indicates that short peptides from residues 1–60, differing from the 70–110 sequence, induce apoptosis, thereby opening the way for identification of new molecular targets to study pathological conditions.https://doi.org/10.1002/2211-5463.13768apoptosisinflammationnerve growth factorpeptidesprodomainproNGF
spellingShingle Marie Anne Makoudjou
Elena Fico
Pamela Rosso
Viviana Triaca
Lucio De Simone
Daniela Rossetti
Franca Cattani
Marcello Allegretti
Paola Tirassa
ProNGF processing in adult rat tissues and bioactivity of NGF prodomain peptides
FEBS Open Bio
apoptosis
inflammation
nerve growth factor
peptides
prodomain
proNGF
title ProNGF processing in adult rat tissues and bioactivity of NGF prodomain peptides
title_full ProNGF processing in adult rat tissues and bioactivity of NGF prodomain peptides
title_fullStr ProNGF processing in adult rat tissues and bioactivity of NGF prodomain peptides
title_full_unstemmed ProNGF processing in adult rat tissues and bioactivity of NGF prodomain peptides
title_short ProNGF processing in adult rat tissues and bioactivity of NGF prodomain peptides
title_sort prongf processing in adult rat tissues and bioactivity of ngf prodomain peptides
topic apoptosis
inflammation
nerve growth factor
peptides
prodomain
proNGF
url https://doi.org/10.1002/2211-5463.13768
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