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

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 β-hairpin peptides.

Role of motor proteins in human cancers

“…Dynamin 2, one member of the dynamin proteins, is an MT-associated force-producing protein involved in producing MT bundles and able to bind and hydrolyze GTP. Dynamin inhibitors like Dynasore, Dyngo-4a, MiTMAB, and Dynole-34–2, target some forms of endocytosis ( Buri et al, 2021 ) . Dynasore can inhibit cell proliferation, migration, and invasion in osteosarcoma cells via STAT3 signaling pathway ( Zhong et al, 2019 ).…”