白细胞介素13诱导Dami细胞分化并下调转录因子c-myc表达

目的：研究重组人白细胞介素13（recombinant human interleukine-13，rhIL-13）对巨核细胞白血病细胞株Dami细胞分化的影响，以及Dumi细胞白细胞介素13受体α1（Interleukine-13 receptor alpha 1，IL-13 Rα1）的表达，探讨IL-13诱导Dami细胞分化的机制。方法：Dumi细胞经无血清培养20小时后，以rhIL-13分别作用不同时间，提取总RNA，用RT—PCR检测Dumi细胞IL-13受体α1 mRNA、GPⅡb mRNA、c-myc mRNA表达水平。流式细胞仪检测在rhIL-13作用下，Dami细胞GPⅡb表达。免疫组化法检测在rhIL-13作用下，Dumi细胞c—myc的表达。图像分析仪对结果进行分析。结果：①Dami细胞表达IL-13 Rα1 mRNA，rhIL-13作用Dumi细胞4小时，IL-13 Rα1 mRNA表达降低，12小时IL-13 Rα1 mRNA表达恢复。②rhIL-13作用Dami细胞后，巨核细胞的分化标志物GPⅡb mRNA和蛋白质表达增加。③rhIL-13作用Dumi细胞，c—myc mRNA和蛋白质表达降低。结论：白细胞介素13下调c—myc表达。     

Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes

Pancreatic -cell dysfunction and insulin resistance are observed in type 2 diabetes. Under diabetic conditions, oxidative stress and ER stress are induced in various tissues, leading to activation of the JNK pathway. This JNK activation suppresses insulin biosynthesis and interferes with insulin action. Indeed, suppression of the JNK pathway in diabetic mice improves insulin resistance and ameliorates glucose tolerance. Thus, the JNK pathway plays a central role in pathogenesis of type 2 diabetes and may be a potential target for diabetes therapy.     

MLP (muscle LIM protein) as a stress sensor in the heart

Muscle LIM protein (MLP, also known as cysteine rich protein 3 (CSRP3, CRP3)) is a muscle-specific-expressed LIM-only protein. It consists of 194 amino-acids and has been described initially as a factor involved in myogenesis (Arber et al. Cell 79:221–231, 1994). MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393–403, 1997). At this time, this was the first genetically altered animal model to develop this devastating disease. Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674–2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78–85, 2006; Geier et al. Circulation 107:1390–1395, 2003; Hershberger et al. Clin Transl Sci 1:21–26, 2008; Kn?ll et al. Cell 111:943–955, 2002; Kn?ll et al. Circ Res 106:695–704, 2010; Mohapatra et al. Mol Genet Metab 80:207–215, 2003). Although considerable efforts have been undertaken to unravel the underlying molecular mechanisms—how MLP mutations, either in model organisms or in the human setting cause these diseases are still unclear. In contrast, only precise knowledge of the underlying molecular mechanisms will allow the development of novel and innovative therapeutic strategies to combat this otherwise lethal condition. The focus of this review will be on the function of MLP in cardiac mechanosensation and we shall point to possible future directions in MLP research.     

Germline deletion in a neurofibromatosis type 2 kindred inactivates the NF2 gene and a candidate meningioma locus

Neurofibromatosis type 2 (NF2) is an autosomal dominant diseasewhich predisposes to the development of schwannomas, meningiomas,ependymomas, and juvenile cataracts. The NF2 gene (NF2) hasrecently been isolated and maps to chromosome 22q12 betweenthe loci D22S212 and D22S32. Deletion studies in sporadic andNF2 associated schwannomas and meningiomas, and the presenceof Inactivating mutations in NF2 in patients suggest that itacts as a tumor suppressor gene. A candidate meningioma gene(MEN) has also been isolated from the same Interval. A new highlypolymorphic (CA)n marker, D22S268, which maps very near to NF2,has allowed us to Identify a kindred with three living affectedindividuals, where the disease Is presumably caused by a largegermline deletion. Fluorescence ^{in situ} hybridization and pulsedfield gel electrophoresis confirm the presence of a 700kb deletionwhich includes the neurofllament heavy chain subunit gene locus(NEFH), D22S268, NF2 and the putative MEN gene. The absenceof meningiomas In this pedigree raises doubts as to the existenceof a separate MEN locus In this region. These results supportthe hypothesis that NF2 results from the Inactivation of a tumorsuppressor gene on chromosome 22q.