15 research outputs found
Phorbol Esters Induce Intracellular Accumulation of the Anti-apoptotic Protein PED/PEA-15 by Preventing Ubiquitinylation and Proteasomal Degradation
Phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA)-15 is an anti-apoptotic protein whose expression is increased in several cancer cells and following experimental skin carcinogenesis. Exposure of untransfected C5N keratinocytes and transfected HEK293 cells to phorbol esters (12-O-tetradecanoylphorbol-13-acetate (TPA)) increased PED/PEA-15 cellular content and enhanced its phosphorylation at serine 116 in a time-dependent fashion. Ser-116 --> Gly (PED(S116G)) but not Ser-104 --> Gly (PED(S104G)) substitution almost completely abolished TPA regulation of PED/PEA-15 expression. TPA effect was also prevented by antisense inhibition of protein kinase C (PKC)-zeta and by the expression of a dominant-negative PKC-zeta mutant cDNA in HEK293 cells. Similar to long term TPA treatment, overexpression of wild-type PKC-zeta increased cellular content and phosphorylation of WT-PED/PEA-15 and PED(S104G) but not of PED(S116G). These events were accompanied by the activation of Ca2+-calmodulin kinase (CaMK) II and prevented by the CaMK blocker, KN-93. At variance, the proteasome inhibitor lactacystin mimicked TPA action on PED/PEA-15 intracellular accumulation and reverted the effects of PKC-zeta and CaMK inhibition. Moreover, we show that PED/PEA-15 bound ubiquitin in intact cells. PED/PEA-15 ubiquitinylation was reduced by TPA and PKC-zeta overexpression and increased by KN-93 and PKC-zeta block. Furthermore, in HEK293 cells expressing PED(S116G), TPA failed to prevent ubiquitin-dependent degradation of the protein. Accordingly, in the same cells, TPA-mediated protection from apoptosis was blunted. Taken together, our results indicate that TPA increases PED/PEA-15 expression at the post-translational level by inducing phosphorylation at serine 116 and preventing ubiquitinylation and proteosomal degradation
Asociaci贸n Infrecuente de S铆ndrome de Gitelman de Reciente Diagn贸stico con Proteinuria Glomerular
S铆ndrome de Gitelman es una tubulopat铆a de herencia autos贸mica recesiva cuya alteraci贸n se halla a nivel del cotransportador Na/Cl en el t煤bulo distal, caracterizada por alcalosis metab贸lica, normotensi贸n,hipopotasemia, hipomagnesemia e hipocalciuria. La proteinuria e hiperfiltraci贸n glomerular (sobre todo al inicio de la presentaci贸n cl铆nica) no son manifestaciones caracter铆sticas de esta enfermedad. M脡TODOS:Reporte de Caso.RESULTADOS: Presentamos el caso de una mujer de 25 a帽os con diagn贸stico reciente de S铆ndrome de Gitelman que present贸 hiperfiltraci贸n y proteinuria glomerular por lo que se realiz贸 biopsia renal evidenciando hipertrofiadel aparato yuxtaglomerular y proliferaci贸n mesangial y en microscopia electr贸nica: desprendimiento focalde podocitos compatible con glomeruloesclerosis focal y segmentaria secundaria. CONCLUSI脫N:Este caso de asociaci贸n de la tubulopat铆a con glomerulopat铆a secundaria de presentaci贸n precoz, pone de manifiesto el camino final que recorre esta tubulopat铆a al generar isquemia renal sostenida por aumento dela actividad del sistema renina angiotensina aldosterona. Result贸 de utilidad la biopsia renal y la microscop铆aelectr贸nica para definir pron贸stico y tratamiento en esta paciente.Fil: Gutierrez, R.. Fundaci贸n Favaloro; ArgentinaFil: Fortunato, R. M.. Fundaci贸n Favaloro; ArgentinaFil: Vigliano, Carlos. Fundaci贸n Favaloro; Argentina. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Oficina de Coordinaci贸n Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingenier铆a. Fundaci贸n Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingenier铆a; ArgentinaFil: Toniolo, M.. Centro de Diagnostico Patologico; ArgentinaFil: Nava, A.. Fundaci贸n Favaloro; ArgentinaFil: Espinoza, A.. Fundaci贸n Favaloro; ArgentinaFil: Raffaele P.M.. Fundaci贸n Favaloro; Argentin
A field experiment on climatic and herbivore impacts on post-fire tree regeneration in north-western Patagonia
Effectiveness of individualized lung recruitment strategies at birth: An experimental study in preterm lambs
Respiratory transition at birth involves rapidly clearing fetal lung liquid and preventing efflux back into the lung while aeration is established. We have developed a sustained inflation (SIOPT) individualized to volume response and a dynamic tidal positive end-expiratory pressure (PEEP) (open lun
The Lumbar Interspinous Ligaments in Humans: Anatomical Study and Review of the Literature
Application of non-invasive seismic techniques for the characterisation of a gravity concrete dam
Telegraph antegrade nailing in the treatment of humeral fractures with rotator interval split technique
Heart failure and chronic kidney disease in a registry of internal medicine wards
Background: The aim of the present study was to evaluate the association between heart failure (HF) and chronic kidney disease (CKD) in tertiary care centers using the clinical records of patients enrolled in internal medicine departments.Patients and methods: We used the clinical records of 1380 elderly patients to identify patients with a history of HF and CKD using admission ICD codes and glomerular filtration rate (GFR) formulas. Magnitude and strength of such associations were investigated by univariable and multivariable analysis.Results: Of the 1380 patients enrolled, 27.9% had HF (age 80 \ub1 7, BMI 27 \ub1 6 kg/m2) and 17.4% CKD (age 81 \ub1 7, BMI 26.8 \ub1 6 kg/m2). Both groups were significantly older (P <' 0.0001) with BMI higher than the patients without those diagnosis (P < 0.02). Patients with a history of CKD showed higher non-fasting glycaemia (140 \ub1 86 vs. 125 \ub1 63 mg/dL, P < 0.001). CKD was significantly associated with HF (P < 0.0001). Patients with HF had an estimated GFR lower than patients without HF (P < 0.0001). Comorbidity and severity indices were significantly higher in subjects with HF (P < 0.0001) and CKD (P < 0.0001) than in those without. Multivariable analysis showed a significant association between HF and age (for five years increase OR 1.13, P < 0.009), BMI (for each 3 kg/m2 increase OR 1.15, P < 0.001), GFR (for each decrease of 10 mL/min increase OR 0.92, P < 0.002) and severity index (IS) (for each 0.25 units increase OR 1.43, P < 0.001).Conclusion: HF on admission is strongly associated with CKD, older age, BMI, and SI. These data focus the value of epidemiological studies such REPOSI in identifying and monitoring multimorbidity in elderly