Endocytosis and the Participation of Glycosaminoglycans Are Important to the Mechanism of Cell Death Induced by beta-Hairpin Antimicrobial Peptides

Autor(es):Mostrar menos -

Buri, Marcus Vinicius ^[1] ; Sperandio, Leticia Paulino ^{[2, 3]} ; de Souza, Kamylla F. S. ^[1] ; Antunes, Fernanda ^[3] ; Rezende, Marina Mastelaro ^[1] ; Melo, Carina Mucciolo ^[1] ; Pinhal, Maria A. S. ^{[1, 4]} ; Barros, Carlos C. ^[5] ; Fernig, David G. ^[6] ; Yates, Edwin A. ^{[1, 6]} ; Ide, Jaime S. ^[7] ; Smaili, Soraya S. ^[3] ; Riske, Karin A. ^[8] ; Nader, Helena B. ^[1] ; dos Santos Tersariol, Ivarne Luis ^[1] ; Lima, Marcelo Andrade ^{[1, 9]} ; Judice, Wagner A. S. ^[2] ; Miranda, Antonio ^[8] ; Paredes-Gamero, Edgar J. ^{[1, 10, 11]}

Afiliação do(s) autor(es):Mostrar menos -

^[1] Univ Fed Sao Paulo, Dept Bioquim, BR-04044020 Sao Paulo - Brazil

^[2] Univ Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, BR-08780911 Mogi Das Cruzes, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Farmacol, BR-04044020 Sao Paulo, SP - Brazil

^[4] Fac Med ABC, Dept Bioquim, BR-09060870 Santo Andre, SP - Brazil

^[5] Univ Fed Pelotas, Dept Nutr, BR-96010610 Pelotas, RS - Brazil

^[6] Univ Liverpool, Dept Biochem & Syst Biol, ISMIB, Liverpool L69 7ZB, Merseyside - England

^[7] Yale Univ, Dept Psychiat, Sch Med, New Haven, CT 06519 - USA

^[8] Univ Fed Sao Paulo, Dept Biofis, BR-04044020 Sao Paulo - Brazil

^[9] Keele Univ, Mol & Struct Biosci, Sch Life Sci, Huxley Bldg, Keele ST5 5BG, Staffs - England

^[10] Univ Fed Mato Grosso do Sul, Fac Ciencias Farmaceut Alimentos & Nutr, BR-79070900 Campo Grande, MS - Brazil

^[11] Fac Ciencias Farmaceut Alimentos & Nutr FACFAN, Lab Biol Mol & Culturas Celulares, Av Costa & Silva S-N, BR-79070900 Campo Grande, MS - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ACS APPLIED BIO MATERIALS; v. 4, n. 8, p. 6488-6501, AUG 16 2021.
• Citações Web of Science: 0

Resumo

The cytotoxic mode of action of four antimicrobial peptides (AMPs) (gomesin, tachyplesin, protegrin, and polyphemusin) against a HeLa cell tumor model is discussed. A study of cell death by AMP stimulation revealed some similarities, including annexin-V externalization, reduction of mitochondrial potential, insensitivity against inhibitors of cell death, and membrane permeabilization. Evaluation of signaling proteins and gene expression that control cell death revealed wide variation in the responses to AMPs. However, the ability to cross cell membranes emerged as an important characteristic of AMP-dependent cell death, where endocytosis mediated by dynamin is a common mechanism. Furthermore, the affinity between AMPs and glycosaminoglycans (GAGs) and GAG participation in the cytotoxicity of AMPs were verified. The results show that, despite their primary and secondary structure homology, these peptides present different modes of action, but endocytosis and GAG participation are an important and common mechanism of cytotoxicity for beta-hairpin peptides. (AU)

• Processo FAPESP: 13/09068-7 - Ação de moduladores hematopoéticos em células-tronco leucêmicas
• Beneficiário: Edgar Julian Paredes-Gamero
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/22901-5 - Rastreamento de uma única molécula por microscopia fototérmica heterodina de peptídeos antimicrobianos
• Beneficiário: Marcus Vinicius Buri
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 12/20989-4 - Estudo de mecanismos moleculares na diferenciação e morte de células tumorais desencadeados por peptídeos antimicrobianos
• Beneficiário: Marcus Vinicius Buri
• Modalidade de apoio: Bolsas no Brasil - Doutorado