Small Structural Differences in Proline-Rich Decapeptides Have Specific Effects on Oxidative Stress-Induced Neurotoxicity and L-Arginine Generation by Arginosuccinate Synthase

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dc.contributor.authorSilva, Carlos Alberto
dc.contributor.authorSilva, Brenda Rufino
dc.contributor.authorSilva, Julio Cezar Araujo
dc.contributor.authorSilva, Felipe Assumpção da Cunha e
dc.contributor.authorKodama, Roberto Tadashi
dc.contributor.authorSilva, Wilmar Dias da
dc.contributor.authorCosta, Maricilia Silva
dc.contributor.authorPortaro, Fernanda Calheta Vieira
dc.date.accessioned2026-01-28T17:31:41Z
dc.date.available2026-01-28T17:31:41Z
dc.date.issued22024
dc.description.abstractntroduction. The proline-rich decapeptide 10c (Bj-PRO-10c; ENWPHPQIPP) from the Bothrops jararaca snake modulates argininosuccinate synthetase (AsS) activity to stimulate L-arginine metabolite production and neuroprotection in the SH-SY5Y cell line. The relationships between structure, interactions with AsS, and neuroprotection are little known. We evaluated the neuro- protective effects of Bj-PRO-10c and three other PROs (Bn-PRO-10a, <ENWPRPKIPP; Bn-PRO-10a- MK, <ENWPRPKIPPMK; and, Bn-PRO-10c, <ENWPRPKVPP) identified from Bitis nasicornis snake venom, with a high degree of similarity to Bj-PRO-10c, on oxidative stress-induced toxicity in neuronal PC12 cells and L-arginine metabolite generation via AsS activity regulation. Methods. Cell integrity, metabolic activity, reactive oxygen species (ROS) production, and arginase activity were examined after 4 h of PRO pre-treatment and 20 h of H2O2-induced damage. Results. Only Bn-PRO-10a-MK and Bn-PRO-10c restored cell integrity and arginase function under oxidative stress settings, but they did not reduce ROS or cell metabolism. The MK dipeptide in Bn-PRO-10a- MK and valine (V8) in Bn-PRO-10c are important to these effects when compared to Bn-PRO-10a. Bj-PRO-10c is not neuroprotective in PC12 cells, perhaps because of their limited NMDA-type glutamate receptor activity. The PROs interaction analysis on AsS activation can be rated as fol- lows: Bj-PRO-10c > Bn-PRO-10c > Bn-PRO-10a-MK > Bn-PRO-10a. The structure of PROs and their correlations with enzyme activity revealed that histidine (H5) and glutamine (Q7) in Bj-PRO-10c potentiated their affinity for AsS. Conclusions. Our investigation provides the first insights into the structure and molecular interactions of PROs with AsS, which could possibly further their neuropharmacological applications.
dc.description.physical16 p.
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.uriFAPESP: 2023/03608-1
dc.format.mimetypePDF
dc.identifier.affiliationUniversidade do Vale do Paraíba
dc.identifier.affiliationUniversidade Federal do ABC
dc.identifier.affiliationInstituto Butantan
dc.identifier.bibliographicCitationSILVA, C. A. et al. Small Structural Differences in Proline-Rich Decapeptides Have Specific Effects on Oxidative Stress-Induced Neurotoxicity and L-Arginine Generation by Arginosuccinate Synthase. Pharmaceuticals, v. 17, n. 7, p. 1-16, 2024. Disponível em: https://www.mdpi.com/1424-8247/17/7/931.
dc.identifier.doi10.3390/ph17070931
dc.identifier.urihttps://repositorio.univap.br/handle/123456789/1112
dc.language.isoen_US
dc.publisherMDPI
dc.rights.holderPharmaceuticals
dc.subject.keywordNeuroprotective
dc.subject.keywordBioactive peptide
dc.subject.keywordProline-rich peptide
dc.subject.keywordSnake venom
dc.subject.keywordOxidative stress
dc.subject.keywordPC12 cells
dc.titleSmall Structural Differences in Proline-Rich Decapeptides Have Specific Effects on Oxidative Stress-Induced Neurotoxicity and L-Arginine Generation by Arginosuccinate Synthase
dc.typeArtigos de Periódicos

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