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...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2024-04-01
|
Series: | FEBS Open Bio |
Subjects: | |
Online Access: | https://doi.org/10.1002/2211-5463.13768 |
_version_ | 1827294720009699328 |
---|---|
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. |
first_indexed | 2024-04-24T14:06:53Z |
format | Article |
id | doaj.art-b0ab1350e18643218da57bfbfb5c3708 |
institution | Directory Open Access Journal |
issn | 2211-5463 |
language | English |
last_indexed | 2024-04-24T14:06:53Z |
publishDate | 2024-04-01 |
publisher | Wiley |
record_format | Article |
series | FEBS Open Bio |
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 |
work_keys_str_mv | AT marieannemakoudjou prongfprocessinginadultrattissuesandbioactivityofngfprodomainpeptides AT elenafico prongfprocessinginadultrattissuesandbioactivityofngfprodomainpeptides AT pamelarosso prongfprocessinginadultrattissuesandbioactivityofngfprodomainpeptides AT vivianatriaca prongfprocessinginadultrattissuesandbioactivityofngfprodomainpeptides AT luciodesimone prongfprocessinginadultrattissuesandbioactivityofngfprodomainpeptides AT danielarossetti prongfprocessinginadultrattissuesandbioactivityofngfprodomainpeptides AT francacattani prongfprocessinginadultrattissuesandbioactivityofngfprodomainpeptides AT marcelloallegretti prongfprocessinginadultrattissuesandbioactivityofngfprodomainpeptides AT paolatirassa prongfprocessinginadultrattissuesandbioactivityofngfprodomainpeptides |