The role of Pannexin-1 channels and extracellular ATP in the pathogenesis of the human immunodeficiency virus

D’Amico, Daniela; Valdebenito, Silvana; Eugenín, Eliseo A.

doi:10.1007/s11302-021-09817-3

Cited by 4 publications

(1 citation statement)

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“…These three protein families can form surface cellular channels, which communicate the intra‐ and extracellular milieux constituting an essential route for autocrine and paracrine cellular communication (Gaete & Contreras, 2020; Syrjanen et al, 2021). For example, large‐pore channels participate in physiological conditions such as neuronal excitability (Dossi et al, 2018), ATP release in the peripheral nervous system (Wei et al, 2021), hemodynamic responses to hypoxia (Kirby et al, 2021), and pathophysiological conditions such as metabolic inhibition in cardiomyocytes (Kondo et al, 2000), oxidative stress in osteocytes (Hua et al, 2021), and the pathogenesis of the human immunodeficiency virus (D'Amico et al, 2021). We recently demonstrated that the T. cruzi opens the pannexin 1‐formed channel and induces calcium transients necessary to invade rat cardiomyocytes (Barria et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Unnexins: Homologs of innexin proteins in Trypanosomatidae parasites

Güiza

García

Arriagada

et al. 2021

Journal Cellular Physiology

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Large-pore channels, including those formed by connexin, pannexin, innexin proteins, are part of a broad family of plasma membrane channels found in vertebrates and invertebrates, which share topology features. Despite their relevance in parasitic diseases such as Chagas and malaria, it was unknown whether these large-pore channels are present in unicellular organisms. We identified 14 putative proteins in Trypanosomatidae parasites as presumptive homologs of innexin proteins. All proteins possess the canonical motif of the innexin family, a pentapeptide YYQWV, and 10 of them share a classical membrane topology of large-pore channels. A sequence similarity network analysis confirmed their closeness to innexin proteins. A bioinformatic model showed that a homolog of Trypanosoma cruzi (T. cruzi) could presumptively form a stable octamer channel with a highly positive electrostatic potential in the internal cavities and extracellular entrance due to the notable predominance of residues such as Arg or Lys. In vitro dye uptake assays showed that divalent cations-free solution increases YO-PRO-1 uptake and hyperosmotic stress increases DAPI uptake in epimastigotes of T. cruzi. Those effects were sensitive to probenecid. Furthermore, probenecid reduced the proliferation and transformation of T. cruzi. Moreover, probenecid or carbenoxolone increased the parasite sensitivity to antiparasitic drugs commonly used in therapy against Chagas. Our study suggests the existence of innexin homologs in unicellular organisms, which could be protein subunits of new large-pore channels in unicellular organisms.

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