10 results on '"Luz Graciela Cervantes-Perez"'
Search Results
2. The Calcium-Sensing Receptor Increases Activity of the Renal NCC through the WNK4-SPAK Pathway
- Author
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Jonatan Barrera-Chimal, Rocio Bautista, Lorena Rojas-Vega, Luz Graciela Cervantes-Perez, Consuelo Plata, Norma A. Bobadilla, Adrián Rafael Murillo-de-Ozores, Daniela Riccardi, Norma Vázquez, David H. Ellison, María Castañeda-Bueno, Lorenza González-Mariscal, Silvana Bazúa-Valenti, and Gerardo Gamba
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Male ,0301 basic medicine ,Pyrrolidines ,Protein Serine-Threonine Kinases ,Xenopus Proteins ,Transfection ,Receptors, G-Protein-Coupled ,Mice ,Xenopus laevis ,03 medical and health sciences ,Phenethylamines ,medicine ,Animals ,Humans ,Solute Carrier Family 12, Member 3 ,Distal convoluted tubule ,Phosphorylation ,Receptor ,Protein Kinase Inhibitors ,Protein Kinase C ,Adaptor Proteins, Signal Transducing ,Solute Carrier Family 12, Member 1 ,Propylamines ,urogenital system ,Chemistry ,Reabsorption ,Microfilament Proteins ,Sodium ,Imidazoles ,General Medicine ,Apical membrane ,WNK4 ,Cell biology ,Enzyme Activation ,Basic Research ,HEK293 Cells ,030104 developmental biology ,medicine.anatomical_structure ,Nephrology ,Oocytes ,Calcium-sensing receptor ,Carrier Proteins ,Cotransporter ,Receptors, Calcium-Sensing ,Signal Transduction - Abstract
Background Hypercalciuria can result from activation of the basolateral calcium-sensing receptor (CaSR), which in the thick ascending limb of Henle’s loop controls Ca(2+) excretion and NaCl reabsorption in response to extracellular Ca(2+). However, the function of CaSR in the regulation of NaCl reabsorption in the distal convoluted tubule (DCT) is unknown. We hypothesized that CaSR in this location is involved in activating the thiazide-sensitive NaCl cotransporter (NCC) to prevent NaCl loss. Methods We used a combination of in vitro and in vivo models to examine the effects of CaSR on NCC activity. Because the KLHL3-WNK4-SPAK pathway is involved in regulating NaCl reabsorption in the DCT, we assessed the involvement of this pathway as well. Results Thiazide-sensitive (22)Na(+) uptake assays in Xenopus laevis oocytes revealed that NCC activity increased in a WNK4-dependent manner upon activation of CaSR with Gd(3+). In HEK293 cells, treatment with the calcimimetic R-568 stimulated SPAK phosphorylation only in the presence of WNK4. The WNK4 inhibitor WNK463 also prevented this effect. Furthermore, CaSR activation in HEK293 cells led to phosphorylation of KLHL3 and WNK4 and increased WNK4 abundance and activity. Finally, acute oral administration of R-568 in mice led to the phosphorylation of NCC. Conclusions Activation of CaSR can increase NCC activity via the WNK4-SPAK pathway. It is possible that activation of CaSR by Ca(2+) in the apical membrane of the DCT increases NaCl reabsorption by NCC, with the consequent, well known decrease of Ca(2+) reabsorption, further promoting hypercalciuria.
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- 2018
3. The Calcium‐sensing Receptor Increases Activity of the Renal Na‐Cl Cotransporter Through the WNK4‐SPAK Pathway
- Author
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Daniela Riccardi, Luz Graciela Cervantes-Perez, David H. Ellison, Lorenza González-Mariscal, Jonatan Barrera-Chimal, Gerardo Gamba, Silvana Bazúa-Valenti, Adrian R. Murillo-de-Ozpres, María Castañeda-Bueno, Lorena Rojas-Vega, Norma Vázquez, Norma A. Bobadilla, Rocio Bautista, and Consuelo Plata
- Subjects
Na-Cl Cotransporter ,Chemistry ,Genetics ,Biophysics ,Calcium-sensing receptor ,Molecular Biology ,Biochemistry ,Biotechnology ,WNK4 - Published
- 2018
4. Inactivation of SPAK kinase reduces body weight gain in mice fed a high-fat diet by improving energy expenditure and insulin sensitivity
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Gerardo Gamba, Luz Graciela Cervantes-Perez, Ivan Torre-Villalvazo, Armando R. Tovar, Nimbe Torres, Lilia G. Noriega, María Chávez-Canales, José Víctor Jiménez, Norma A. Bobadilla, Claudia Tovar-Palacio, Norma Uribe, and Braulio A Marfil-Garza
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0301 basic medicine ,Male ,medicine.medical_specialty ,Physiology ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Mice, Transgenic ,Biology ,Protein Serine-Threonine Kinases ,Body weight ,Diet, High-Fat ,Weight Gain ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Gene Knock-In Techniques ,Gene Silencing ,Protein kinase A ,Cells, Cultured ,Kinase ,Insulin sensitivity ,medicine.disease ,Obesity ,Dietary Fats ,Thermogenin ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Metabolic syndrome ,Insulin Resistance ,Cotransporter ,Energy Metabolism - Abstract
The STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) controls the activity of the electroneutral cation-chloride cotransporters (SLC12 family) and thus physiological processes such as modulation of cell volume, intracellular chloride concentration [Cl−]i, and transepithelial salt transport. Modulation of SPAK kinase activity may have an impact on hypertension and obesity, as STK39, the gene encoding SPAK, has been suggested as a hypertension and obesity susceptibility gene. In fact, the absence of SPAK activity in mice in which the activating threonine in the T loop was substituted by alanine (SPAK-KI mice) is associated with decreased blood pressure; however its consequences in metabolism have not been explored. Here, we fed wild-type and homozygous SPAK-KI mice a high-fat diet for 17 wk to evaluate weight gain, circulating substrates and hormones, energy expenditure, glucose tolerance, and insulin sensitivity. SPAK-KI mice exhibit resistance to HFD-induced obesity and hepatic steatosis associated with increased energy expenditure, higher thermogenic activity in brown adipose tissue, increased mitochondrial activity in skeletal muscle, and reduced white adipose tissue hypertrophy mediated by augmented whole body insulin sensitivity and glucose tolerance. Our data reveal a previously unrecognized role for the SPAK kinase in the regulation of energy balance, thermogenesis, and insulin sensitivity, suggesting that this kinase could be a new drug target for the treatment of obesity and the metabolic syndrome.
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- 2017
5. Modulation of NCC activity by low and high K+ intake: insights into the signaling pathways involved
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María Castañeda-Bueno, Luz Graciela Cervantes-Perez, Erika Moreno, Lorena Rojas-Vega, Gerardo Gamba, Isidora Arroyo-Garza, and Norma Vázquez
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Male ,medicine.medical_specialty ,Physiology ,Aldosterone metabolism ,Protein Serine-Threonine Kinases ,Biology ,Ste20-related proline-alanine-rich kinase ,Excretion ,Mice ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Solute Carrier Family 12, Member 3 ,Distal convoluted tubule ,Phosphorylation ,distal convoluted tubule ,Mice, Knockout ,aldosterone ,Aldosterone ,urogenital system ,Angiotensin II ,Potassium, Dietary ,Articles ,with-no-lysine kinase 4 ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Models, Animal ,Signal transduction ,Cotransporter ,Signal Transduction - Abstract
Modulation of Na+-Cl− cotransporter (NCC) activity is essential to adjust K+ excretion in the face of changes in dietary K+ intake. We used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K+ diets. SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K+-citrate diets for 4 days. The low-K+ diet decreased and high-K+ diet increased plasma aldosterone levels, but both diets were associated with increased phosphorylation of NCC (phospho-NCC, Thr44/Thr48/Thr53) and phosphorylation of SPAK/oxidative stress responsive kinase 1 (phospho-SPAK/OSR1, Ser383/Ser325). The effect of the low-K+ diet on SPAK phosphorylation persisted in WNK4 knockout and SPAK knockin mice, whereas the effects of ANG II on NCC and SPAK were lost in both mouse colonies. This suggests that for NCC activation by ANG II, integrity of the WNK4/SPAK pathway is required, whereas for the low-K+ diet, SPAK phosphorylation occurred despite the absence of WNK4, suggesting the involvement of another WNK (WNK1 or WNK3). Additionally, because NCC activation also occurred in SPAK knockin mice, it is possible that loss of SPAK was compensated by OSR1. The positive effect of the high-K+ diet was observed when the accompanying anion was citrate, whereas the high-KCl diet reduced NCC phosphorylation. However, the effect of the high-K+-citrate diet was aldosterone dependent, and neither metabolic alkalosis induced by bicarbonate, nor citrate administration in the absence of K+ increased NCC phosphorylation, suggesting that it was not due to citrate-induced metabolic alkalosis. Thus, the accompanying anion might modulate the NCC response to the high-K+ diet.
- Published
- 2014
6. Disruption of the WNK/SPAK pathway attenuates angiotensin II, but enhances aldosterone‐induced hypertension (1136.3)
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Luz Graciela Cervantes-Perez, Isidora Arroyo, Gerardo Gamba, María Castañeda-Bueno, Norma A. Bobadilla, Dario R. Alessi, and Norma Vázquez
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chemistry.chemical_compound ,medicine.medical_specialty ,Aldosterone ,Endocrinology ,chemistry ,Internal medicine ,Genetics ,medicine ,Molecular Biology ,Biochemistry ,Angiotensin II ,Biotechnology - Published
- 2014
7. SPAK's kinase activity and WNK4 expression are not essential for NCC activation under low K + diet
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Luz Graciela Cervantes-Perez, Gerardo Gamba, and María Castañeda-Bueno
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Chemistry ,Genetics ,Kinase activity ,Molecular Biology ,Biochemistry ,Biotechnology ,WNK4 ,Cell biology - Published
- 2013
8. Sexual dimorphic regulation of NCC involves higher SPAK and NCC phosphorylation in female rodents
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María Castañeda-Bueno, Luz Graciela Cervantes-Perez, Gerardo Gamba, Lorena Rojas-Vega, Luis A. Reyes-Castro, Hector Damian Hernandez, and Elena Zambrano
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Sexual dimorphism ,Genetics ,Phosphorylation ,Biology ,Molecular Biology ,Biochemistry ,Biotechnology ,Cell biology - Published
- 2013
9. Activation of the renal Na+:Cl- cotransporter by angiotensin II is a WNK4-dependent process
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Luciana Morla, Norma A. Bobadilla, Alain Doucet, Sheila Kantesaria, Gerardo Gamba, Norma Vázquez, María Castañeda-Bueno, Luz Graciela Cervantes-Perez, Norma Uribe, and Dario R. Alessi
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medicine.medical_specialty ,Pseudohypoaldosteronism ,Immunoblotting ,Blood Pressure ,Biology ,Protein Serine-Threonine Kinases ,Xenopus Proteins ,Kidney ,Real-Time Polymerase Chain Reaction ,chemistry.chemical_compound ,Mice ,Internal medicine ,Renin–angiotensin system ,Renin ,medicine ,Animals ,Distal convoluted tubule ,Phosphorylation ,Aldosterone ,DNA Primers ,Mice, Knockout ,Multidisciplinary ,Reabsorption ,urogenital system ,Angiotensin II ,Infusion Pumps, Implantable ,Diet, Sodium-Restricted ,Biological Sciences ,WNK1 ,Immunohistochemistry ,Sodium Chloride Symporters ,WNK4 ,Endocrinology ,medicine.anatomical_structure ,chemistry - Abstract
Pseudohypoaldosteronism type II is a salt-sensitive form of hypertension with hyperkalemia in humans caused by mutations in the with-no-lysine kinase 4 (WNK4). Several studies have shown that WNK4 modulates the activity of the renal Na + Cl − cotransporter, NCC. Because the renal consequences of WNK4 carrying pseudoaldosteronism type II mutations resemble the response to intravascular volume depletion (promotion of salt reabsorption without K + secretion), a condition that is associated with high angiotensin II (AngII) levels, it has been proposed that AngII signaling might affect WNK4 modulation of the NCC. In Xenopus laevis oocytes, WNK4 is required for modulation of NCC activity by AngII. To demonstrate that WNK4 is required in the AngII-mediated regulation of NCC in vivo, we used a total WNK4-knockout mouse strain (WNK4 −/− ). WNK4 mRNA and protein expression were absent in WNK4 −/− mice, which exhibited a mild Gitelman-like syndrome, with normal blood pressure, increased plasma renin activity, and reduced NCC expression and phosphorylation at T-58. Immunohistochemistry revealed normal morphology of the distal convoluted tubule with reduced NCC expression. Low-salt diet or infusion of AngII for 4 d induced phosphorylation of STE20/SPS1-related proline/alanine-rich kinase (SPAK) and of NCC at S-383 and T-58, respectively, in WNK4 +/+ but not WNK4 −/− mice. Thus, the absence of WNK4 in vivo precludes NCC and SPAK phosphorylation promoted by a low-salt diet or AngII infusion, suggesting that AngII action on the NCC occurs via a WNK4-SPAK–dependent signaling pathway. Additionally, stimulation of aldosterone secretion by AngII, but not by a high-K + diet, was impaired in WNK4 −/− mice.
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- 2012
10. WNK4 is required for the Angiotensin II activation of NCC in vivo
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María Castañeda-Bueno, Norma A. Bobadilla, Norma Vázquez, Dario R. Alessi, Luz Graciela Cervantes-Perez, and Gerardo Gamba
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In vivo ,Chemistry ,Genetics ,Pharmacology ,Molecular Biology ,Biochemistry ,Angiotensin II ,Biotechnology ,WNK4 - Published
- 2012
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