The broad expression pattern of the G protein-coupled P2Y receptors has demonstrated that these receptors are fundamental determinants in many physiological responses, including neuromodulation, vasodilation, inflammation, and cell migration. P2Y receptors couple either Gq or Gi upon activation, thereby activating different signaling pathways. Ionotropic ATP (P2X) receptors bind extracellular nucleotides, a signal which is transduced within the P2X protein complex into a cation channel opening, which usually leads to intracellular calcium concentration elevation. As such, this family of proteins initiates or shapes several cellular processes including synaptic transmission, gene expression, proliferation, migration, and apoptosis. The ever-growing range of applications for antibodies in the last 30 years attests to their major role in medicine and biological research. Antibodies have been used as therapeutic tools in cancer and inflammatory diseases, as diagnostic reagents (flow cytometry, ELISA, and immunohistochemistry, to name a few applications), and in widespread use in biological research, including Western blot, immunoprecipitation, and ELISPOT. In this article, we will showcase several of the advances that scientists around the world have achieved using the line of antibodies developed at Alomone Labs for P2Y and P2X receptors.
While progress has been made in treating cancer, cytotoxic chemotherapeutic agents are still the most widely used drugs and are associated with severe side-effects. Drugs that target unique molecular signalling pathways are needed for treating cancer with low or no intrinsic toxicity to normal cells. Our goal is to target hypoxic tumours and specifically the hypoxia inducible factor (HIF) pathway for the development of new cancer therapies. To this end, we have previously developed benzopyran-based HIF-1 inhibitors such as arylsulfonamide KCN1. However, KCN1 and its earlier analogs have poor water solubility, which hamper their applications. Herein, we describe a series of KCN1 analogs that incorporate a morpholine moiety at various positions. We found that replacing the benzopyran group of KCN1 with a phenyl group with a morpholinomethyl moiety at the para positions had minimal effect on potency and improved the water solubility of two new compounds by more than 10-fold compared to KCN1, the lead compound. 相似文献
Human T lymphocytes, rerosetted with sheep erythrocytes in the presence of adenosine, yield two subpopulations: a major one (ER), still capable of forming E rosettes; and a minor nonrosetting (ES) one. The two subpopulations differed in their proliferative responses to various mitogens. ER cells responded well to galactose oxidase (GO), soybean agglutinin (SBA), and phytohemagglutinin (PHA) but responded poorly to concanavalin A (Con A). The response of ES cells was poor to GO and SBA, intermediate to PHA, and significantly high to Con A. The different response of ER and ES subsets to Con A was not greatly affected by adherent cells, but an enhancing effect on the proliferation of ES cells to Con A was observed when prostaglandin synthesis was inhibited by indomethacin. Addition of ES cells to ER cells in a ratio of 1:5 resulted in an enhanced synergistic effect of Con A-induced proliferation. A soluble mitogenic factor released from Con A-activated T cells appeared involved in this enhanced proliferation. This factor (ESF) was produced only by the minor T-cell subpopulation which is sensitive to adenosine (ES). The induction of ESF was not dependent on the addition of adherent cells and required 72 hr of incubation for its production. ESF was mitogenic to nonactivated and Con A-activated PBL as well as to T, ER, and ES subpopulations. Following incubation of ER cells with ESF, a suppressor factor (ERSF) was produced which abolished the mitogenic activity of ESF. Differences between these factors and a known mediator like Interleukin-2 (IL-2) and suppressor factors are discussed. 相似文献
Based on previous observations indicating a role for collagen peptides in eliciting a positive feedback for collagen biosynthesis, this study was initiated to elucidate the effect of non-crosslinked collagen on granulation tissue formation in dermal excision wounds. The wounds were treated with either non-crosslinked or crosslinked native collagen, or left untreated as controls. Granulation tissue was analyzed for collagen type I mRNA, for levels of interstitial collagen and for the number of blood vessels. The results indicated significant increases in procollagen type I mRNA, in interstitial collagen, in the number of blood vessels and in epithelial advance in the non-crosslinked collagen-treated wounds relative to the untreated controls. It is assumed that the presence of non-crosslinked collagen in a healing wound enhances both procollagen type I biosynthesis and the repair process of dermal wounds, due to the more readily released collagen peptides derived from this exogenous collagen dressing. 相似文献
During neuron development, the biosynthetic needs of the axon initially outweigh those of dendrites. However, although a localized role for the early secretory pathway in dendrite development has been observed, such a role in axon growth remains undefined. We therefore studied the localization of Sar1, a small GTPase that controls ER export, during early stages of neuronal development that are characterized by selective and robust axon growth. At these early stages, Sar1 was selectively targeted to the axon where it gradually concentrated within varicosities in which additional proteins that function in the early secretory pathway were detected. Sar1 targeting to the axon followed axon specification and was dependent on localized actin instability. Changes in Sar1 expression levels at these early development stages modulated axon growth. Specifically, reduced expression of Sar1, which was initially only detectable in the axon, correlated with reduced axon growth, where as overexpression of Sar1 supported the growth of longer axons. In support of the former finding, expression of dominant negative Sar1 inhibited axon growth. Thus, as observed in lower organisms, mammalian cells use temporal and spatial regulation of endoplasmic reticulum exit site (ERES) to address developmental biosynthetic demands. Furthermore, axons, such as dendrites, rely on ERES targeting and assembly for growth. 相似文献
Induction of the luminescence system of the marine luminous bacteriumVibrio harveyi growing on a solid medium was studied. The induction occurred when the total number of cells per square centimeter of solid medium approached 104 cells (i.e., either 100 colonies consisting of 100 cells per each colony or 1 colony with about 104 cells). The preinduction period and number of cells per colony at the time of induction decreased as the number of colonies per cm2 increased. The ecological significance of the induction of the luminescence system on solid medium is discussed. 相似文献
Conditions for producing stable transverse volume discharges in freon-containing media (CCl4/air mixtures at a pressure of P=0.1?2 kPa) are studied. It is shown that a transverse discharge produced in the CCl4/air=(1–2)/0.03 kPa mixture at a moderate discharge voltage (Uch=8–15 kV) and an interelectrode distance of d=2.2 cm is a selective source of C2(d3Πg-a3Πu) 468.0-and 516.5-nm radiation and C(2p-3s) 247.9-nm radiation. The brightness of the C2(d-a) band is comparable with that of the N2(C-B) 337.1-and 357-nm bands. The transverse discharge in CCl4 is of interest for generating pulsed emission via the d-a transitions of C2 molecules in the blue-green region of the visible spectrum. 相似文献