Cellscience最新文献

At present there is no cure for advanced prostate cancer once it progresses to an androgen independent stage. Hormonal therapy, radiotherapy, and chemotherapy all have limited durations of efficacy for men diagnosed with androgen independent disease and patients will succumb over a period of several months to two years. The androgen receptor (AR) has been suspected to play an important role in the mechanism of progression to androgen independence. This is because the AR is a transcription factor that 'normally' mediates the effects of androgen to regulate expression of genes involved in proliferation and survival of prostate cells. Thus identifying and characterizing the proteins that interact with the AR to facilitate an activated receptor is of critical importance. Proteomic approaches such as isotope-coded affinity tags (ICAT), isotope Tags for Relative and Absolute Quantification (iTRAQ)(TM), Stable Isotope Labeling with Amino acids in Cell culture (SILAC), Tandem Affinity Purification (TAP) of tagged proteins (TAP-tag) and Multidimensional Protein Identification Technology (MudPIT) provide large scale unbiased strategies and have not been previously applied to identify proteins that interact with the AR. Here an example of the power of these proteomic approaches to identify potential therapeutic targets for prostate cancer is provided. Application of MudPIT identified 82 peptides in endogenous complexes immunoprecipitated with the AR from prostate cancer cells. Identification of these novel proteins may ultimately lead to the development of better therapies for the treatment or prevention of advanced prostate cancer.

Type 2 Diabetes results from a complex physiologic process that includes the pancreatic beta cells, peripheral glucose uptake in muscle, the secretion of multiple cytokines and hormone-like molecules from adipocytes, hepatic glucose production, and likely the central nervous system. Consistent with the complex web of physiologic defects, the emerging picture of the genetics will involve a large number of risk susceptibility genes, each individually with relatively small effect (odds ratios below 1.2 in most cases). The challenge for the future will include cataloging and confirming the genetic risk factors, and understanding how these risk factors interact with each other and with the known environmental and lifestyle risk factors that increase the propensity to type 2 diabetes.

Because of the predominant role of skeletal muscle in insulin-stimulated clearance of blood glucose, understanding mechanisms for increasing the ability of muscle to respond to insulin could potentially lead to novel strategies for treatment or prevention of diabetes. Recently, the AMP activated protein kinase (AMPK) has emerged as a promising candidate for potentiation of insulin action. Several antidiabetic drugs have been shown to activate AMPK, cellular stresses such as exercise that increase AMPK activity also increase insulin action, and several downstream targets of AMPK seem to be involved in regulation of insulin action. Although the picture is currently incomplete, it seems possible that AMPK or one of its effectors is a positive regulator of insulin-stimulated glucose transport. In addition to discussion of the latest literature regarding AMPK and insulin action, this review includes a non-technical summary for students, academics from other fields, interested professionals, and the general public.

Following certain patterns of electrical activity the strength of conventional chemical synapses in many areas of the mammalian brain can be subject to long-term modifications. Such modifications have been extensively characterised and are hypothesised to form the basis of learning and memory. A recent study in Science now shows that activity-dependent long-term modifications may also occur in the strength of mammalian electrical synapses. This raises the enticing possibility that electrical synapses might also contribute to neural plasticity and challenges the notion that in the mammalian CNS they are a simple mechanism for 'hardwiring' discrete neuronal populations.