Contribution of Connexin Hemichannels to the Decreases in Cell Viability Induced by Linoleic Acid in the Human Lens Epithelial Cells (HLE-B3)

作者：Vania Figueroa, Oscar Jara, Carolina A. Oliva, Marcelo Ezquer, Fernando Ezquer, Mauricio A. Retamal, Agustı́n D. Martı́nez, Guillermo A. Altenberg, Aníbal A. Vargas · 发表于：Frontiers in Physiology · 年份：2020 · DOI：10.3389/fphys.2019.01574 · 被引用次数：16 · 研究领域：Connexins and lens biology、Heme Oxygenase-1 and Carbon Monoxide、Biochemical effects in animals

Connexin (Cx) proteins form hemichannels that a allow bidirectional flow of ions and metabolites between the cytoplasm and extracellular space. Under physiological conditions, hemichannels have a very low probability of opening, but in certain pathologies, hemichannels activity can increase and induce and/or accelerate cell death. Several mechanisms control hemichannels activity, including phosphorylation and oxidation (i.e., S-nitrosylation). Recently, the effect of polyunsaturated fatty acids (PUFAs) such as linoleic acid (LA), were found to modulate Cxs. It has been seen that LA increase cell death in bovine and human lens cells. The lens is a structure allocated in the eye that highly depends on Cx for the metabolic coupling between its cells, a condition necessary for its transparency. Therefore, we hypothesized that LA induces lens cells death by modulating hemichannel activity. In this work, we characterized the effect of LA on hemichannel activity and survival of HLE-B3 cells (a human lens epithelial cell line). We found that HLE-B3 cells expresses Cx43, Cx46 and Cx50 and can form functional hemichannels in their plasma membrane. The extracellular exposure to 10-50 µM of LA increases hemichannels activity (dye uptake) in a concentration-dependent manner, which was reduced by Cx-channel blockers, such as the Cx-mimetic peptide Gap27 and TATGap19, La3+, carbenoxolone and the Akt kinase inhibitor. Additionally, LA increases intracellular calcium, which is attenuated in t...