Bibliographic Details
Title: |
Small Structural Differences in Proline-Rich Decapeptides Have Specific Effects on Oxidative Stress-Induced Neurotoxicity and L-Arginine Generation by Arginosuccinate Synthase. |
Authors: |
Alberto-Silva, Carlos, da Silva, Brenda Rufino, da Silva, Julio Cezar Araujo, Cunha e Silva, Felipe Assumpção da, Kodama, Roberto Tadashi, da Silva, Wilmar Dias, Costa, Maricilia Silva, Portaro, Fernanda Calheta Vieira |
Source: |
Pharmaceuticals (14248247); Jul2024, Vol. 17 Issue 7, p931, 16p |
Subject Terms: |
MOLECULAR structure, PEPTIDES, PROLINE, ARGININE, CELL metabolism, SNAKE venom, VENOM |
Abstract: |
Introduction. 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 neuroprotective effects of Bj-PRO-10c and three other PROs (Bn-PRO-10a, 2O2-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 follows: 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. [ABSTRACT FROM AUTHOR] |
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Database: |
Complementary Index |
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