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Juan Carlos Saez

Physiology P. Universidad Catolica de Chile, Santiago, Región Metropolitana, Chile 
connexin, pannexin
"Juan Saez"


Regulation and function of connexin and pannexin based membrane channels in cells of the nervous and immune and systems and their involvement in pathological conditions.

In collaboration with students (undergraduate and graduate), Chilean and international researchers, we study the regulation and functional roles of plasma membrane channels formed by connexins (Cxs) or pannexins (Pxs), which are proteins expressed by most cell types in vertebrates. They constitute channels termed gap junction channels (GJCs) and hemichannels (HCs) or connexons. GJCs communicate the cytoplasm of contacting cells and HCs communicate the intra and extra cellular compartments. We also study the interactions of Cx and Px based channels with purinergic receptors (P2). All these channels are crucial in the coordination of numerous cellular responses in diverse tissues. Our studies focus mainly in normal and aberrant functioning of the nervous and immune systems. We use primary cultures, cell lines and animal models of inflammatory diseases or diseases that activate and evolve with an inflammatory response. We analyze the effects of neurotransmitters, hormones and pro-inflammatory conditions on the extent of intercellular communication and cell death mediated by the channels of interest. Biochemical, biophysical, cellular and molecular biological techniques are used to study the expression, post-transcriptional modifications and intercellular trafficking of Cxs and Pxs. In collaboration with industries (R+D), we are currently developing chemical compounds that affect these channels to control the deleterious consequences of pro-inflammatory conditions. Since regeneration is the last step of inflammatory responses and shares numerous features with tissue ontogeny, we also perform research on the regulation and function of the channels of interest in cell growth and differentiation. The final goal of the latter is to gain knowledge on the role of GJCs and HCs in tumorogenesis.
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Vega JL, Gutiérrez C, Rojas M, et al. (2023) Contribution of large-pore channels to inflammation induced by microorganisms. Frontiers in Cell and Developmental Biology. 10: 1094362
Abbott AC, García IE, Villanelo F, et al. (2023) Expression of KID syndromic mutation Cx26S17F produces hyperactive hemichannels in supporting cells of the organ of Corti. Frontiers in Cell and Developmental Biology. 10: 1071202
Guo A, Zhang H, Li H, et al. (2022) Inhibition of connexin hemichannels alleviates neuroinflammation and hyperexcitability in temporal lobe epilepsy. Proceedings of the National Academy of Sciences of the United States of America. 119: e2213162119
Lucero CM, Marambio-Ruiz L, Balmazabal J, et al. (2022) TNF-α Plus IL-1β Induces Opposite Regulation of Cx43 Hemichannels and Gap Junctions in Mesangial Cells through a RhoA/ROCK-Dependent Pathway. International Journal of Molecular Sciences. 23
Palacios-Prado N, Soto PA, López X, et al. (2022) Endogenous pannexin1 channels form functional intercellular cell-cell channels with characteristic voltage-dependent properties. Proceedings of the National Academy of Sciences of the United States of America. 119: e2202104119
López X, Palacios-Prado N, Güiza J, et al. (2021) A physiologic rise in cytoplasmic calcium ion signal increases pannexin1 channel activity via a C-terminus phosphorylation by CaMKII. Proceedings of the National Academy of Sciences of the United States of America. 118
Güiza J, Arriagada J, Rodríguez L, et al. (2021) Anti-parasitics drugs that modulates non-selective channels formed by connexins or pannexins. Biochimica Et Biophysica Acta. Molecular Basis of Disease. 166188
López X, Escamilla R, Fernández P, et al. (2020) Stretch-Induced Activation of Pannexin 1 Channels Can Be Prevented by PKA-Dependent Phosphorylation. International Journal of Molecular Sciences. 21
Choi EJ, Palacios-Prado N, Sáez JC, et al. (2020) Identification of Cx45 as a Major Component of GJs in HeLa Cells. Biomolecules. 10
Recabal A, Fernández P, López S, et al. (2020) The FGF2-induced tanycyte proliferation involves a connexin 43 hemichannel/purinergic-dependent pathway. Journal of Neurochemistry
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