Autor:	Alberto-Silva C; Natural and Humanities Sciences Center (CCNH), Experimental Morphophysiology Laboratory, Federal University of ABC (UFABC), São Bernardo do Campo, SP, Brazil., Pantaleão HQ; Natural and Humanities Sciences Center (CCNH), Experimental Morphophysiology Laboratory, Federal University of ABC (UFABC), São Bernardo do Campo, SP, Brazil., da Silva BR; Natural and Humanities Sciences Center (CCNH), Experimental Morphophysiology Laboratory, Federal University of ABC (UFABC), São Bernardo do Campo, SP, Brazil., da Silva JCA; Natural and Humanities Sciences Center (CCNH), Experimental Morphophysiology Laboratory, Federal University of ABC (UFABC), São Bernardo do Campo, SP, Brazil., Echeverry MB; Center for Mathematics, Computation and Cognition (CMCC), Federal University of ABC, São Bernardo do Campo, SP, Brazil.
Jazyk:	angličtina
Zdroj:	The journal of venomous animals and toxins including tropical diseases [J Venom Anim Toxins Incl Trop Dis] 2024 Feb 09; Vol. 30, pp. e20230043. Date of Electronic Publication: 2024 Feb 09 (Print Publication: 2024).
DOI:	10.1590/1678-9199-JVATITD-2023-0043
Abstrakt:	Background: The bioactive peptides derived from snake venoms of the Viperidae family species have been promising as therapeutic candidates for neuroprotection due to their ability to prevent neuronal cell loss, injury, and death. Therefore, this study aimed to evaluate the cytoprotective effects of a synthetic proline-rich oligopeptide 7a (PRO-7a; Methods: Both cells were pre-treated for four hours with different concentrations of PRO-7a, submitted to H 2 O 2 -induced damage for 20 h, and then the oxidative stress markers were analyzed. Also, two independent neuroprotective mechanisms were investigated: a) L-arginine metabolite generation via argininosuccinate synthetase (AsS) activity regulation to produce agmatine or polyamines with neuroprotective properties; b) M1 mAChR receptor subtype activation pathway to reduce oxidative stress and neuron injury. Results: PRO-7a was not cytoprotective in C6 cells, but potentiated the H 2 O 2 -induced damage to cell integrity at a concentration lower than 0.38 μM. However, PRO-7a at 1.56 µM, on the other hand, modified H 2 O 2 -induced toxicity in PC12 cells by restoring cell integrity, mitochondrial metabolism, ROS generation, and arginase indirect activity. The α-Methyl-DL-aspartic acid (MDLA) and L-N ^Ω -Nitroarginine methyl ester (L-Name), specific inhibitors of AsS and nitric oxide synthase (NOS), which catalyzes the synthesis of polyamines and NO from L-arginine, did not suppress PRO-7a-mediated cytoprotection against oxidative stress. It suggested that its mechanism is independent of the production of L-arginine metabolites with neuroprotective properties by increased AsS activity. On the other hand, the neuroprotective effect of PRO-7a was blocked in the presence of dicyclomine hydrochloride (DCH), an M1 mAChR antagonist. Conclusions: For the first time, this work provides evidence that PRO-7a-induced neuroprotection seems to be mediated through M1 mAChR activation in PC12 cells, which reduces oxidative stress independently of AsS activity and L-arginine bioavailability. Competing Interests: Competing interests: Not applicable.
Databáze:	MEDLINE
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