Navegando por Palavras-chave "intracellular pH"

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    Regulation of Na+/H+ exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells
    (Amer Physiological Soc, 2009-12-01) Carraro-Lacroix, Luciene R. [UNIFESP]; Malnic, Gerhard; Girardi, Adriana C. C.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Carraro-Lacroix LR, Malnic G, Girardi AC. Regulation of Na+/H+ exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells. Am J Physiol Renal Physiol 297: F1647-F1655, 2009. First published September 23, 2009; doi:10.1152/ajprenal.00082.2009.-The gut incretin hormone glucagon-like peptide 1 (GLP-1) is released in response to ingested nutrients and enhances insulin secretion. in addition to its insulinotropic properties, GLP-1 has been shown to have natriuretic actions paralleled by a diminished proton secretion. We therefore studied the role of the GLP-1 receptor agonist exendin-4 in modulating the activity of Na+/H+ exchanger NHE3 in LLC-PK1 cells. We found that NHE3-mediated Na+-dependent intracellular pH (pH(i)) recovery decreased similar to 50% after 30-min treatment with 1 nM exendin-4. Pharmacological inhibitors and cAMP analogs that selectively activate protein kinase A (PKA) or the exchange protein directly activated by cAMP (EPAC) demonstrated that regulation of NHE3 activity by exendin-4 requires activation of both cAMP downstream effectors. This conclusion was based on the following observations: 1) the PKA antagonist H-89 completely prevented the effect of the PKA activator but only partially blocked the exendin-4-induced NHE3 inhibition; 2) the MEK1/2 inhibitor U-0126 abolished the effect of the EPAC activator but only diminished the exendin-4-induced NHE3 inhibition; 3) combination of H-89 and U-0126 fully prevented the effect of exendin-4 on NHE3; 4) no additive effect in the inhibition of NHE3 activity was observed when exendin-4, PKA, and EPAC activators were used together. Mechanistically, the inhibitory effect of exendin-4 on pHi recovery was associated with an increase of NHE3 phosphorylation. Conversely, this inhibition took place without changes in the surface expression of the transporter. We conclude that GLP-1 receptor agonists modulate sodium homeostasis in the kidney, most likely by affecting NHE3 activity.
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    Voltage-Gated Proton Channel in Human Glioblastoma Multiforme Cells
    (Amer Chemical Soc, 2016) Ribeiro-Silva, Luisa [UNIFESP]; Queiroz, Fernanda Oliveira [UNIFESP]; Brito da Silva, Annielle Mendes [UNIFESP]; Hirata, Aparecida Emiko [UNIFESP]; Arcisio-Miranda, Manoel [UNIFESP]
    Solid tumors tend to have a more glycolytic metabolism leading to an accumulation of acidic metabolites in their cytosol, and consequently, their intracellular pH (pH(i)) turns critically lower if the cells do not handle the acid excess. Recently, it was proposed that the voltage gated proton channels (H(v)1) can regulate the pH(i) in several cancers. Here we report the functional expression of voltage gated proton channels in a human glioblastoma multiforme (GBM) cell line, the most common and lethal brain tumor. T98G cells presented an outward, slow activating voltage-dependent proton current, which was also Delta pH-dependent and inhibited by ZnCl2, characterizing it as being conducted by H(v)1 channels. Furthermore, blocking H(v)1 channels with ZnCl2 significantly reduced the pH(i), cell survival, and migration, indicating an important role for H(v)1 for tumor proliferation and progression in GBM. Overall, our results suggest that H(v)1 channels can be a new therapeutic target for GBM.