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

• Published in: ACS applied bio materials Vol. 4; no. 8; pp. 6488 - 6501
• Main Authors: Buri, Marcus Vinicius, Sperandio, Letícia Paulino, de Souza, Kamylla F. S, Antunes, Fernanda, Rezende, Marina Mastelaro, Melo, Carina Mucciolo, Pinhal, Maria A. S, Barros, Carlos C, Fernig, David G, Yates, Edwin A, Ide, Jaime S, Smaili, Soraya S, Riske, Karin A, Nader, Helena B, Luis dos Santos Tersariol, Ivarne, Lima, Marcelo Andrade, Judice, Wagner A. S, Miranda, Antonio, Paredes-Gamero, Edgar J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16-08-2021
• Subjects: Antimicrobial Peptides; Cell Death; Endocytosis; Glycosaminoglycans; HeLa Cells; Humans; glycosaminoglycans; endocytosis; translocation; cell death; antimicrobial peptides; β-hairpin peptides
• ISSN: 2576-6422; 2576-6422
• DOI: 10.1021/acsabm.1c00390

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 β-hairpin peptides.