Changes in Expression of Connexin 32, Bile Canaliculus-Like Structures,and Localization of Alkaline Phosphatase in Primary Cultures of Fetal Rat Hepatocytes

We devised an experimental design in primary cultures of fetal rat hepatocytes for studying hepatocyte differentiation over a short period. In the present study, hepatocytes were first cultured for 3 days in dexamethasone-supplemented medium and then for an additional 3 days in dexamethasone- or epidermal growth factor-supplemented medium. In hepatocytes cultured continuously in dexamethasone-supplemented medium, the expression of connexin 32 increased and bile canaliculus-like structures and localization of alkaline phosphatase in the plasma membrane around bile canaliculus-like structures were maintained. Few cells incorporated bromodeoxyuridine. On the other hand, in most of the hepatocytes cultured in epidermal growth factor-supplemented medium, the expression of connexin 32 was minimally recognized, bile canaliculus-like structures were shortened or eliminated, and alkaline phosphatase was localized as numerous fine spots throughout the cytoplasm. More than 20% of all hepatocytes incorporated bromodeoxyuridine.The present study suggests that in hepatocytes, there is a close relationship among connexin 32 expression, the maintenance of bile canaliculus-like structures, and the localization of alkaline phosphatase to the plasma membrane around the bile canaliculus-like structures, and this indicates that the present experimental model is useful for studying hepatocyte differentiation over a short period.     

急性染镉对大鼠心肌细胞闰盘超微结构和连接蛋白43表达的影响及黄芪甲苷的拮抗作用

目的:观察急性染镉对大鼠心肌细胞闰盘超微结构和连接蛋白43(Cx43)表达的影响,探讨黄芪甲苷的保护机制.方法:SD大鼠随机分为正常组、镉处理组、镉加黄芪甲苷处理组,取心室肌组织,分别作光镜、透射电镜观察和免疫组织化学检测.结果:与正常组相比,镉组心肌细胞连接蛋白43的表达量明显降低,心肌纤维和闰盘超微结构破坏严重;而镉加黄芪甲苷组心肌细胞连接蛋白43的表达量较镉组显著增加,心肌纤维和闰盘超微结构的损伤也明显减轻.结论:镉能破坏心肌细胞闰盘超微结构,影响连接蛋白43的表达及分布,黄芪甲苷能在一定程度上拮抗镉对心肌细胞闰盘超微结构和连接蛋白43的毒性损伤.     

Connexins in neurons and glia：targets for intervention in disease and injury

Both neurons and glia throughout the central nervous system are organized into networks by gap junctions. Among glia, gap junctions facilitate metabolic homeostasis and intercellular communication. Amo...     

关附甲素抗氧化和抗房颤作用

研究关附甲素(Guanfu base A,GFA)的抗房颤和抗氧化作用。大鼠尾静脉注射乙酰胆碱-氯化钙混合液(Ca Cl210 mg/m L,Ach 66μg/m L),连续7 d建立房颤模型。SD大鼠分为正常组、模型组、GFA治疗组(6 mg/kg,12 mg/kg)、胺碘酮(Amiodarone,Ami)治疗组(50 mg/kg)以及洛伐他汀(Lovastatin,Lov)治疗组(10 mg/kg)。测定大鼠房颤持续时间和有效不应期(AERP),用实时荧光定量PCR方法和Western blot方法测定氧化应激相关基因表达,试剂盒测定抗氧化酶的活性。结果显示:与模型组相比,GFA(6 mg/kg,12 mg/kg,po)治疗4 d后能缩短房颤持续时间,延长AERP,超氧化物歧化酶的活力提高,丙二醛含量明显下降。心房肌p22phox、p47phox、p67phox、gp91phox表达下调,膜Rac-1与胞浆Rac-1比值显著下降,缝隙连接蛋白(connexin40)表达升高。提示GFA(6 mg/kg,12 mg/kg)能有效抑制房颤引起的大鼠心房氧化应激损害,抑制房颤发生。     

Impaired compensatory beta‐cell function and growth in response to high‐fat diet in LDL receptor knockout mice

In this study, we investigated the effect of low density lipoprotein receptor (LDLr) deficiency on gap junctional connexin 36 (Cx36) islet content and on the functional and growth response of pancreatic beta-cells in C57BL/6 mice fed a high-fat (HF) diet. After 60 days on regular or HF diet, the metabolic state and morphometric islet parameters of wild-type (WT) and LDLr−/− mice were assessed. HF diet-fed WT animals became obese and hypercholesterolaemic as well as hyperglycaemic, hyperinsulinaemic, glucose intolerant and insulin resistant, characterizing them as prediabetic. Also they showed a significant decrease in beta-cell secretory response to glucose. Overall, LDLr−/− mice displayed greater susceptibility to HF diet as judged by their marked cholesterolaemia, intolerance to glucose and pronounced decrease in glucose-stimulated insulin secretion. HF diet induced similarly in WT and LDLr−/− mice, a significant decrease in Cx36 beta-cell content as revealed by immunoblotting. Prediabetic WT mice displayed marked increase in beta-cell mass mainly due to beta-cell hypertrophy/replication. Nevertheless, HF diet-fed LDLr−/− mice showed no significant changes in beta-cell mass, but lower islet–duct association (neogenesis) and higher beta-cell apoptosis index were seen as compared to controls. The higher metabolic susceptibility to HF diet of LDLr−/− mice may be explained by a deficiency in insulin secretory response to glucose associated with lack of compensatory beta-cell expansion.     

缝隙连接在血管内皮和平滑肌细胞中的作用及其与高血压的关系

细胞间的直接通讯--缝隙连接在控制和协调血管功能方面起重要作用。缝隙连接是沟通相邻细胞质膜的唯一一类通道,为离子、小分子代谢物质、第二信使等细胞间信号分子的直接交换提供一个通道。血管内皮细胞和平滑肌细胞表达多种类型缝隙连接蛋白(connexin,Cx),多种Cx 在心血管系统中的共同表达并协调一致地工作,对心血管系统的发育、平滑肌和内皮细胞功能的整合、以及对血管壁细胞功能协调等起着重要作用。在血管发生疾病时Cx表达相应发生改变,以与缝隙连接调节血管紧张度和动脉血压的作用相一致。本综述讨论了在血管内皮和平滑肌细胞在生理和病理情况下(以高血压为例)缝隙连接对血管结构和功能的影响。     

兔心房及肺静脉肌袖组织结构和Cx40、Cx43表达的增龄性改变

目的通过研究家兔心房和肺静脉肌袖(PVs)的组织结构及缝隙连接蛋白(cx)的增龄性改变,探讨增龄与房颤的关系,为增龄是否是房颤发生的主要或独立危险因素提供实验依据。方法以家兔为研究对象,测量各组家兔心电图的P波时限,分离不同年龄组家兔心房、肺静脉肌袖组织,用组织化学和免疫组化的方法检测胶原纤维和缝隙连接蛋白的表达。结果 P波的Pa、Pmax、Pmin和Pd随着增龄均显著延长,差异有统计学意义(PO.05);心肌间质中胶原纤维容积分数随着增龄逐渐增多.差异有统计学意义(P0.05);心房和肺静脉肌袖组织随着增龄Cx43的表达量呈明显的下降趋势,差异有统计学意义(P0.05)。结论P波时限、胶原纤维含量和缝隙连接蛋白均存在增龄性改变。     

The Role of GJD2(Cx36) in Refractive Error Development

Refractive errors are common eye disorders characterized by a mismatch between the focal power of the eye and its axial length. An increased axial length is a common cause of the refractive error myopia (nearsightedness). The substantial increase in myopia prevalence over the last decades has raised public health concerns because myopia can lead to severe ocular complications later in life. Genomewide association studies (GWAS) have made considerable contributions to the understanding of the genetic architecture of refractive errors. Among the hundreds of genetic variants identified, common variants near the gap junction delta-2 (GJD2) gene have consistently been reported as one of the top hits. GJD2 encodes the connexin 36 (Cx36) protein, which forms gap junction channels and is highly expressed in the neural retina. In this review, we provide current evidence that links GJD2(Cx36) to the development of myopia. We summarize the gap junctional communication in the eye and the specific role of GJD2(Cx36) in retinal processing of visual signals. Finally, we discuss the pathways involving dopamine and gap junction phosphorylation and coupling as potential mechanisms that may explain the role of GJD2(Cx36) in refractive error development.     

间隙连接蛋白43突变与皮肤疾病相关性研究

间隙连接蛋白(Cx)在保证细胞间物质信息传递及维持皮肤屏障稳态方面发挥着重要作用,其基因突变,甚至表达水平异常均会引起多种疾病,严重影响患者生活质量。在编码人类Cx家族的21个基因中,与Cx基因突变相关的临床伴随疾病至少有14种。其中,Cx43分布最广,不仅在大多数器官组织中均有报道,也是伤口愈合、皮肤角质化,以及皮肤肿瘤发展等重要生理病理过程中的关键调控节点。本文总结了近年来Cx43基因(GJA1)在皮肤屏障中的作用、GJA1基因突变相关皮肤疾病及其潜在致病机制这几个快速发展领域中的研究成果,以期为Cx43临床伴发疾病防治及相关研究提供参考。