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Eur J Pharmacol ; 890: 173649, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33049300

RESUMO

Cathelicidins are a class of gene-encoded multifunctional factors in host defence systems. They have recently attracted a great deal of attention as promising drug candidates. Cathelicidins are well studied in vertebrates, yet no studies have been reported concerning gecko cathelicidin. Recently, we identified a novel cathelicidin from Gekko japonicus, Gj-CATH3. Unlike most cathelicidins, Gj-CATH3 exhibits potent antioxidant activity in vitro. Unfortunately, slight toxicity and high synthesis cost restrict its application. Thus, we designed a series of Gj-CATH3 analogues for development of short peptides with improved cell selectivity. Functional analysis showed that two truncated peptides, Gj-CATH3-(38-42)-peptide and Gj-CATH3-(33-42)-peptide, exhibited excellent antioxidant activity against ABTS and DPPH free radicals. Further, cytotoxicity and hemolytic activities were observably lower compared to Gj-CATH3. Interestingly, both peptides also demonstrate significant wound healing properties in a mouse model with full-thickness skin wounds. The peptides induce HaCaT cell proliferation and prevent decreases in SOD activity and increases of MDA concentration in injured-skin tissue. This report is the first to address cathelicidin from reptilia that exhibit potent wound healing activity. Our research will enrich understanding of cathelicidin biological functions, and provide a theoretical basis for its clinical application.


Assuntos
Anti-Infecciosos/química , Antioxidantes/química , Antioxidantes/farmacologia , Catelicidinas/química , Catelicidinas/farmacologia , Peptídeos/química , Peptídeos/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/toxicidade , Antioxidantes/toxicidade , Catelicidinas/genética , Catelicidinas/toxicidade , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Hemólise/efeitos dos fármacos , Humanos , Lagartos , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Peptídeos/toxicidade , Pele/efeitos dos fármacos , Pele/lesões , Pele/patologia , Superóxido Dismutase/metabolismo
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