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

Author(s):Show less -

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]}

Affiliation:Show less -

^[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

• Document type: Journal article
• Source: ACS APPLIED BIO MATERIALS; v. 4, n. 8, p. 6488-6501, AUG 16 2021.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 13/09068-7 - Action of hematopoietic modulators in leukemic stem cells
• Grantee: Edgar Julian Paredes-Gamero
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/22901-5 - Photothermal heterodyne image Microscopy single molecule tracking of antimicrobial peptide
• Grantee: Marcus Vinicius Buri
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 12/20989-4 - Molecular mechanisms studies in differentiation and cell death by antimicrobial peptides using leukemic and adenocarcinoma cells
• Grantee: Marcus Vinicius Buri
• Support Opportunities: Scholarships in Brazil - Doctorate