RESUMO
Platelet activation is a complex balance of positive and negative signaling pathways. Several protein kinase C (PKC) isoforms are expressed in human platelets. They are a major regulator of platelet granule secretion, activation and aggregation activity. One of those isoforms is the PKCδ isozyme, it has a central yet complex role in platelets such as opposite signaling functions depending on the nature of the agonist, it concentration and pathway. In fact, it has been shown that PKCδ has an overall negative influence on platelet function in response to collagen, while, following PAR stimulation, PKCδ has a positive effect on platelet function. Understanding the crucial role of PKCδ in platelet functions is recently emerging in the literature, therefore, further investigations should shed light into its specific role in hemostasis. In this review, we focus on the different roles of PKCδ in platelet activation, aggregation and thrombus formation.
Assuntos
Coagulação Sanguínea/fisiologia , Plaquetas/enzimologia , Ativação Plaquetária/fisiologia , Proteína Quinase C-delta/fisiologia , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Colágeno/farmacologia , Grânulos Citoplasmáticos/metabolismo , Humanos , Isoenzimas/sangue , Isoenzimas/química , Isoenzimas/fisiologia , Camundongos , Fosforilação , Ativação Plaquetária/efeitos dos fármacos , Glicoproteínas da Membrana de Plaquetas/metabolismo , Conformação Proteica , Domínios Proteicos , Proteína Quinase C-delta/sangue , Proteína Quinase C-delta/química , Processamento de Proteína Pós-Traducional , Transporte Proteico , Pseudópodes/ultraestrutura , Receptores Ativados por Proteinase/sangue , Transdução de Sinais , Trombina/farmacologiaRESUMO
The purpose of this study was to investigate whether common variants in inflammatory and immune response genes influence inflammatory bowel disease (IBD) risk among Moroccan patients. Using a candidate gene approach, 10 single-nucleotide polymorphisms mapping on six genes (MIF_rs755622, TNFA_rs1800629, IL6_rs2069840, IL6R_rs2228145, IL6ST_rs2228044, IL17A (rs2275913, rs4711998, rs7747909, rs8193036, rs3819024)) were assessed in 510 subjects grouped in 199 IBD and 311 healthy controls. Genotyping was performed with the TaqMan allelic discrimination technology. The results were analyzed using PLINK software. The frequency of allele A for TNFA rs1800629 was significantly higher in ulcerative colitis (UC) patients compared with controls (30.16 vs 16.72%; P=0.0005; odds ratio (OR)=2.15; 95% confidence interval (CI)=1.39-3.32). Statistically significant association to UC was also found under dominant AA+AG vs GG (OR=1.85, 95% CI=1.07-3.21; P=0.02) and recessive models (OR=8.38; 95% CI=2.86-24.53; P=0.0001). In the same way, an association of TNFA rs1800629 variant was observed with IBD under recessive model AA vs AG+GG (OR=4.10; 95% CI=1.56-10.76; P=0.004). No evidence of significant associations was found for the remaining investigated polymorphisms. Our data suggest that TNFA gene promoter polymorphism participates in determining IBD susceptibility in Moroccan patients.
Assuntos
Colite Ulcerativa/genética , Doenças Inflamatórias Intestinais/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Idoso , Colite Ulcerativa/imunologia , Doença de Crohn/genética , Citocinas/genética , Citocinas/imunologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/imunologia , Masculino , Pessoa de Meia-Idade , Marrocos , Receptores de Citocinas/genética , Receptores de Citocinas/imunologia , Fator de Necrose Tumoral alfa/imunologia , Adulto JovemRESUMO
The protein kinase C (PKC) family has been implicated in several physiological processes regulating platelet activation. Each isoform of PKC expressed on platelets, may have a positive and/or negative role depending on the nature and concentration of the agonist. Mice lacking PKCα show much reduced thrombus formation in vivo, while PKCθ(-/-) showed inhibition of aggregation in response to PAR4. On the other hand, PKCδ by associating with Fyn, inhibits platelet aggregation. In addition, PKCß by interacting with its receptor RACK1 has been implicated in the primary phases of signaling via the αIIbß3 and finally PKCÉ appears to be involved in platelet function downstream GPVI. The present review discusses the latest observations relevant to the role of individual PKC isoforms in platelet activation and thrombus formation.
Assuntos
Proteína Quinase C/fisiologia , Trombose/genética , Animais , Humanos , Isoenzimas , Camundongos , Camundongos Knockout , Ativação Plaquetária/genética , Agregação Plaquetária/genética , Proteína Quinase C/genéticaRESUMO
Diabetes is recognized as a major public health problem responsible for early morbidity and mortality with a worldwide prevalence in permanent increase. The type II diabetes once called non-insulin dependent diabetes, accounts for about 90 % of all forms of diabetes and is characterized by abnormalities that affect insulin secretion and insulin action and thus, induces hyperglycemia. The aim of this work is to study the involvement of a key enzyme of glycolysis, glyceraldehyde-3-phosphate dehydrogenase in type 2 diabetes. This work includes a biochemical, kinetic studies, and the study of the expression of GAPDH in subjects with type 2 diabetes. From our study, we could classify the diabetic subjects into two categories: the first one, consisting of subjects in whom GAPDH has a specific activity and an electrophoretic profile similar to healthy subjects, and the second one, in which there is an inhibition of GAPDH. Our results suggest that, in 60 % of our patients with type 2 diabetes, a reversible inhibition of GAPDH is observed. This inhibition is probably mediated by the ionic interaction with the erythrocyte membrane protein, band 3.
