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Signalling of protein kinase B and expression of cyclooxygenase in early phases of diabetic nephropathy
Ždychová, Jana ; Komers, Radko (advisor) ; Haluzík, Martin (referee) ; Matoušovic, Karel (referee) ; Škrha, Jan (referee)
Introduction: Renal hypertrophy, extracellular matrix accumulation, aItered apoptosis as well as changes in regional hemodynamics have been implicated in the pathophysiology of nephropathy in diabetes mellitus (DM). On the molecular level the detailed mechanisms for development of diabetic nephropathy (DN) have becn intensively studied. Insulin induces a variety of biologicaI effects in a number of cell types via phosphatidylinositol-3 kinase (PI3K)/Akt kinase signaling pathway. Considering multiple function of Akt that incIude potentiaIly hannful pro-growth effects mediated by mTOR and cyclooxygenas-2 (COX-2), as well as protective effects mediated by endotheliaI nitric oxide synthase (eNOS), it is possible that aIterations in activities of Akt may play role in the pathophysiology ofDN. Renal corticaI activity and expression of Akt, its down-strearn effectors mTOR, eNOS, and "C<JIX-:Z. as well as PTEN, an endogenous Akt inhibitor, were investigated in streptozotocin (STZ): diabetic rats as a model of Type 1 DM with different levels of glycenůc control, and in Zucker ~d.iabetic fatty rats, a model ofDM2, and in nondiabetic rats as controls. Methods: Akt activity was measured by kinase assay. Protein expressions were measured by .immunoblotting and immunohistochemistry in renal cortex of 4- and 12- week old...
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Signalling of protein kinase B and expression of cyclooxygenase in early phases of diabetic nephropathy
Ždychová, Jana ; Komers, Radko (advisor) ; Haluzík, Martin (referee) ; Matoušovic, Karel (referee) ; Škrha, Jan (referee)
Introduction: Renal hypertrophy, extracellular matrix accumulation, aItered apoptosis as well as changes in regional hemodynamics have been implicated in the pathophysiology of nephropathy in diabetes mellitus (DM). On the molecular level the detailed mechanisms for development of diabetic nephropathy (DN) have becn intensively studied. Insulin induces a variety of biologicaI effects in a number of cell types via phosphatidylinositol-3 kinase (PI3K)/Akt kinase signaling pathway. Considering multiple function of Akt that incIude potentiaIly hannful pro-growth effects mediated by mTOR and cyclooxygenas-2 (COX-2), as well as protective effects mediated by endotheliaI nitric oxide synthase (eNOS), it is possible that aIterations in activities of Akt may play role in the pathophysiology ofDN. Renal corticaI activity and expression of Akt, its down-strearn effectors mTOR, eNOS, and "C<JIX-:Z. as well as PTEN, an endogenous Akt inhibitor, were investigated in streptozotocin (STZ): diabetic rats as a model of Type 1 DM with different levels of glycenůc control, and in Zucker ~d.iabetic fatty rats, a model ofDM2, and in nondiabetic rats as controls. Methods: Akt activity was measured by kinase assay. Protein expressions were measured by .immunoblotting and immunohistochemistry in renal cortex of 4- and 12- week old...
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Genetic predisposition to diabetic nephropathy
Romžová, Marianna ; Černá, Marie (advisor) ; Kalousová, Marta (referee) ; Komers, Radko (referee)
Diabetic nephropathy is major microvascular complication leading to end stage renal silure and CVD associated death in diabetic patients, thus accounts for increased mortality and morbidity in these patients. Clinical definition of DN is presence of proteinuria over 0.5 g per 24h. It occurs in 15 - 30 % of type 1 diabetic patients after 20 years of diabetes duration, whereas prevalence in type 2 diabetes is more variable, ranging form 5 to 40 %. The fact that only subset of diabetic patients eventually develop DN despite long-term severe chronic hyperglycemia, together with the evidence of familial clustering of DN and various ethnic/racial prevalence of DN indicie hereditary predisposition to DN, independent form predisposition to diabetes mellitus. The conception of combination of several "bad" genes and environmental factors, such are glycemic control, blood pressure control or hypertension, was established as model of DN inheritance. To reveal genetic markers, implicated in renal diabetic complications, two main strategies have been used in DN research - linkage analysis and population based association studies. Present work shows new results of the investigation on DN predisposition markers. Several polymorphisms in the genes encoding transcription factor NFB and its inhibitor IB, transcription factor...
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