1. Mechanisms involved in the cytoprotective effects of Lonomia obliqua venom on human endometrial stromal cells.
- Author
-
de Almeida Schneider, Raquel, Barros Terraciano, Paula, Zanon, Pamela, Quandt, Letícia, Zanini Gotardi, Debora Helena, Alves Garcez, Tuane Nerissa, Santi, Lucélia, Beys da Silva, Walter Orlando, Sereno Montenegro, Ivan, Yates, John, Almeida Guimarães, Jorge, Pandolfi Passos, Eduardo, and Berger, Markus
- Subjects
- *
CYTOPROTECTION , *ENDOMETRIUM , *STROMAL cells , *RECURRENT miscarriage , *VENOM , *ION exchange chromatography , *EMBRYO implantation , *ANIMAL migration - Abstract
The pathophysiology of recurrent pregnancy loss (RPL) involves deficiencies in the proliferation and migration capacities of endometrial stromal cells (hESCs), which impair embryo implantation and development. Since animal venoms are rich source of bioactive molecules, we aimed to characterize the cytoprotective effects of Lonomia obliqua venom on hESCs. hESCs were isolated from endometrial biopsies and the mechanisms of L. obliqua venomous secretions on cell viability, proliferation and migration were characterized. Venom components were identified by chromatography and proteomic analyses. L. obliqua venom induced hESC proliferation, viability and migration in a dose-dependent manner, both in the presence and absence of serum. By ion-exchange chromatography, one fraction enriched in cytoprotective components and devoid of hemotoxins was obtained. Venom proteome identified at least six protein classes with potential cytoprotective properties (hemolins, lipocalins, hemocyannins, antiviral proteins, antimicrobial peptides, and protease inhibitors). L. obliqua venom protected hESCs from oxidative insult. Cytoprotection was also related to nitric oxide and PKC-ERK-activation and down-regulation of cAMP-PKA-dependent pathways that control cell proliferation. L. obliqua venom-induced hESC viability, proliferation and migration occurs mainly by protecting against oxidative damage and activating ERK. Thus, L. obliqua venom components are promising pharmacological tools to understand the underlying mechanisms of hESC deficiency in RPL. [Display omitted] • Endometrial stromal cell (hESC) proliferation and migration capacities are deficient in recurrent pregnancy loss (RPL). • By venom proteomics we identified at least six protein classes able to protect hESCs. • L. obliqua venom components protected hESCs from oxidative insult. • Cytoprotective mechanisms involve nitric oxide, PKC-ERK-activation and cAMP-PKA-downregulation. • L. obliqua venom components are promising tools to understand the underlying mechanisms of hESC deficiency in RPL. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF