哮喘是一种常见且易反复发作的气道免疫炎症疾病,多种细胞及其组分可共同参与并促进其病理过程。气道炎症是哮喘的基本特征,可引起气道高反应,常表现为炎症细胞的增加及炎性细胞的浸润。磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase,...哮喘是一种常见且易反复发作的气道免疫炎症疾病,多种细胞及其组分可共同参与并促进其病理过程。气道炎症是哮喘的基本特征,可引起气道高反应,常表现为炎症细胞的增加及炎性细胞的浸润。磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase,PI3K)的活化可导致丝氨酸/苏氨酸蛋白激酶(serine/threonine protein kinase,Akt)的募集、磷酸化,活化的Akt可磷酸化一系列细胞内蛋白从而介导下游反应。近年来,越来越多的研究表明PI3K/Akt信号通路与哮喘气道炎症紧密相关,可通过多机制影响哮喘及其气道炎症的进展。本文就近年来PI3K/Akt信号通路参与哮喘气道炎症反应的发生发展进行综述,为研究哮喘的临床治疗及平喘药物的开发提供理论基础。展开更多
AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models...AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models of nonalcoholic fatty liver were established by high-fat diet feeding. The expression of total and phosphorylated P13K and Akt proteins in hepatocytes was determined by Western blotting. Degree of fat accumulation in liver was measured by hepatic triglyceride. Mitochondrial number and size were determined using quantitative morphometric analysis under transmission electron microscope. The permeability of the outer mitochondrial membrane was assessed by determining the potential gradient across this membrane.RESULTS:After Wistar rats were fed with high-fat diet for 16 wk,their hepatocytes displayed an accumulation of fat (103.1 ± 12.6 vs 421.5 ± 19.7,P < 0.01),deformed mitochondria (9.0% ± 4.3% vs 83.0% ± 10.9%,P < 0.05),and a reduction in the mitochondrial membrane potential (389.385% ± 18.612% vs 249.121% ± 13.526%,P < 0.05). In addition,the expression of the phosphorylated P13K and Akt proteins in hepatocytes was reduced,as was the expression of the anti-apoptotic protein Bcl-2,while expression of the pro-apoptotic protein caspase-3 was increased. When animals were treated with pharmacological inhibitors of P13K or Akt,instead of high-fat diet,a similar pattern of hepatocellular fat accumulation,mitochondrial impairment,and change in the levels of PI3K,Akt,Bcl-2 was observed. CONCLUSION:High-fat diet appears to inhibit the PI3K/Akt signaling pathway,which may lead to hepa-tocellular injury through activation of the mitochondrial membrane pathway of apoptosis.展开更多
文摘哮喘是一种常见且易反复发作的气道免疫炎症疾病,多种细胞及其组分可共同参与并促进其病理过程。气道炎症是哮喘的基本特征,可引起气道高反应,常表现为炎症细胞的增加及炎性细胞的浸润。磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase,PI3K)的活化可导致丝氨酸/苏氨酸蛋白激酶(serine/threonine protein kinase,Akt)的募集、磷酸化,活化的Akt可磷酸化一系列细胞内蛋白从而介导下游反应。近年来,越来越多的研究表明PI3K/Akt信号通路与哮喘气道炎症紧密相关,可通过多机制影响哮喘及其气道炎症的进展。本文就近年来PI3K/Akt信号通路参与哮喘气道炎症反应的发生发展进行综述,为研究哮喘的临床治疗及平喘药物的开发提供理论基础。
基金Supported by The Natural Science Foundation of Heilongjiang Province, No. 2005-13
文摘AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models of nonalcoholic fatty liver were established by high-fat diet feeding. The expression of total and phosphorylated P13K and Akt proteins in hepatocytes was determined by Western blotting. Degree of fat accumulation in liver was measured by hepatic triglyceride. Mitochondrial number and size were determined using quantitative morphometric analysis under transmission electron microscope. The permeability of the outer mitochondrial membrane was assessed by determining the potential gradient across this membrane.RESULTS:After Wistar rats were fed with high-fat diet for 16 wk,their hepatocytes displayed an accumulation of fat (103.1 ± 12.6 vs 421.5 ± 19.7,P < 0.01),deformed mitochondria (9.0% ± 4.3% vs 83.0% ± 10.9%,P < 0.05),and a reduction in the mitochondrial membrane potential (389.385% ± 18.612% vs 249.121% ± 13.526%,P < 0.05). In addition,the expression of the phosphorylated P13K and Akt proteins in hepatocytes was reduced,as was the expression of the anti-apoptotic protein Bcl-2,while expression of the pro-apoptotic protein caspase-3 was increased. When animals were treated with pharmacological inhibitors of P13K or Akt,instead of high-fat diet,a similar pattern of hepatocellular fat accumulation,mitochondrial impairment,and change in the levels of PI3K,Akt,Bcl-2 was observed. CONCLUSION:High-fat diet appears to inhibit the PI3K/Akt signaling pathway,which may lead to hepa-tocellular injury through activation of the mitochondrial membrane pathway of apoptosis.
