Home About us Contact
|
Home About us Contact | ||
|
|
||
Intracellular Molecules (intracellular + molecule)
Selected AbstractsModulation of astrocyte P2Y1 receptors by the carboxyl terminal domain of the gap junction protein Cx43GLIA, Issue 2 2008Eliana Scemes Abstract Gap junction proteins, connexins, provide intercellular channels that allow ions and small signaling molecules to be transmitted to adjacent coupled cells. Besides this function, it is becoming apparent that connexins also exert channel-independent effects, which are likely mediated by processes involving protein,protein interactions. Although a number of connexin interacting proteins have been identified, only little is known about the functional consequences of such interactions. We have previously shown that deletion of the astrocytic gap junction protein, connexin43 (Cx43) causes a right-ward shift in the dose-response curve to P2Y1R agonists and decreased P2Y1R expression levels. To evaluate whether these changes were due to reduced gap junctional communication or to protein,protein interactions, Cx43-null astrocytes were transfected with full-length Cx43 and Cx43 domains, and P2Y1R function and expression levels evaluated. Results indicate that restoration of P2Y1R function is independent of gap junctional communication and that the Cx43 carboxyl terminus spanning the SH3 binding domain (260,280) participates in the rescue of P2Y1R pharmacological behavior (shifting to the left the P2Y1R dose-response curve) without affecting its expression levels. These results suggest that the Cx43 carboxyl-terminus domain provides a binding site for an intracellular molecule, most likely a member of the c-Src tyrosine kinase family, which affects P2Y1R-induced calcium mobilization. It is here proposed that a nonchannel function of Cx43 is to serve as a decoy for such kinases. Such modulation of P2Y1R is expected to influence several neural cell functions, especially under inflammation and neurodegenerative disorders where expression levels of Cx43 are decreased. © 2007 Wiley-Liss, Inc. [source] Bid-dependent generation of oxygen radicals promotes death receptor activation,induced apoptosis in murine hepatocytesHEPATOLOGY, Issue 2 2004Wen-Xing Ding Activation of tumor necrosis factor receptor 1 or Fas leads to the generation of reactive oxygen species, which are important to the cytotoxic effects of tumor necrosis factor , (TNF-,) or Fas ligand. However, how these radicals are generated following receptor ligation is not clear. Using primary hepatocytes, we found that TNF-, or anti,Fas antibody,induced burst of oxygen radicals was mainly derived from the mitochondria. We discovered that Bid,a pro-death Bcl-2 family protein activated by ligated death receptors,was the main intracellular molecule signaling the generation of the radicals by targeting to the mitochondria and that the majority of oxygen radical production was dependent on Bid. Reactive oxygen species contributed to cell death and caspase activation by promoting FLICE-inhibitory protein degradation and mitochondrial release of cytochrome c. For the latter part, the oxygen radicals did not affect Bak oligomerization but instead promoted mitochondrial cristae reorganization and membrane lipid peroxidation. Antioxidants could reverse these changes and therefore protect against TNF-, or anti,Fas-induced apoptosis. In conclusion, our studies established the signaling pathway from death receptor engagement to oxygen radical generation and determined the mechanism by which reactive oxygen species contributed to hepatocyte apoptosis following death receptor activation. (HEPATOLOGY 2004;40:403,413.) [source] Perforin expression in peripheral blood lymphocytes and skin-infiltrating cells in patients with lichen planusBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2004L. Prpi, Massari Summary Background, Current evidence suggests that lichen planus is a T-cell-mediated autoimmune disease in which cytotoxic mechanisms have been poorly investigated. Objectives, We investigated the expression of perforin in subpopulations of peripheral blood lymphocytes (PBL) in exacerbation and remission phases of the disease as well as in skin lesions. Methods, We performed a simultaneous detection of perforin (intracellular molecule) and cell surface antigens on PBL by flow cytometry, and skin lesions were investigated by immunohistochemistry. Results, The most interesting finding was a significant increase of perforin expression in cytotoxic T lymphocytes (CD3+ perforin+ cells) in the exacerbation phase of disease (P < 0·05), which was mostly located in the CD8+ subpopulation (CD8+ perforin+) (P < 0·01). Using immunohistochemistry we confirmed the infiltration of T lymphocytes in skin lesions, especially of CD4+ and CD8+ phenotypes, compared with uninvolved (P < 0·05) and healthy skin (P < 0·01). The expression of perforin was also significantly higher in lesional skin compared with nonlesional and healthy skin (P < 0·05). Conclusions, Our results clearly show the upregulation of perforin expression in peripheral blood as well as in lesions of patients with lichen planus and therefore suggest an important role for perforin in this autoimmune disease. [source] Cover Picture: Electrophoresis 14/2008ELECTROPHORESIS, Issue 14 2008Article first published online: 23 JUL 200 Issue 14 is a regular issue including an Emphasis Section offering a series of 9 papers on ,Microfluidics and Miniaturization". These 9 research papers report on various topics including studying single DNA molecules, selective release of intracellular molecules on the single cell level, isoelectric focusing of proteins in an ordered micropillar array, sample stream focusing in a microchip, integrated microfluidic system for sensing infectious viral disease, EOF in annulus and rectangular channels, confinement effects on monolith morphology, accumulation and filtering of nanoparticles in microchannels, and carbon nanotubes disposable detectors. [source] A multifaceted imbalance of T cells with regulatory function characterizes type 1 autoimmune hepatitis,,HEPATOLOGY, Issue 3 2010Silvia Ferri Immunotolerance is maintained by regulatory T cells (Tregs), including CD4+CD25hi, CD8+CD28,, ,,, and CD3+CD56+ [natural killer T (NKT)] cells. CD4+CD25hi cells are impaired in children with autoimmune hepatitis (AIH). Little is known about Tregs in adults with AIH. The aim of this study was to investigate the frequency and function of Treg subsets in adult patients with AIH during periods of active disease and remission. Forty-seven AIH patients (16 with active disease and 31 in remission) and 28 healthy controls were studied. Flow cytometry was used to evaluate surface markers and function-related intracellular molecules in ,,, CD8+CD28,, NKT, and CD4+CD25hi cells. CD4+CD25hi T cell function was determined by the ability to suppress proliferation and interferon gamma (IFN-,) production by CD4+CD25, target cells. Liver forkhead box P3,positive (FOXP3+) cells were sought by immunohistochemistry. In AIH patients, particularly during active disease, CD4+CD25hi T cells were fewer, expressed lower levels of FOXP3, and were less effective at inhibiting target cell proliferation versus healthy controls. Moreover, although the numbers of CD8+CD28, T cells were similar in AIH patients and healthy controls, NKT cells were numerically reduced, especially during active disease, and produced lower quantities of the immunoregulatory cytokine interleukin-4 versus controls. In contrast, ,, T cells in AIH patients were more numerous versus healthy controls and had an inverted V,1/V,2 ratio and higher IFN-, and granzyme B production; the latter was correlated to biochemical indices of liver damage. There were few FOXP3+ cells within the portal tract inflammatory infiltrate. Conclusion: Our data show that the defect in immunoregulation in adult AIH is complex, and ,, T cells are likely to be effectors of liver damage. (HEPATOLOGY 2010) [source] Facets of heat shock protein 70 show immunotherapeutic potentialIMMUNOLOGY, Issue 1 2003Stephen M. Todryk Summary Amongst the families of intracellular molecules that chaperone and assist with the trafficking of other proteins, notably during conditions of cellular stress, heat shock protein (hsp) 70 is one of the most studied. Although its name suggests that expression is exclusively induced during cellular hyperthermia, members of the hsp70 family of proteins can be constitutively expressed and/or induced by a range of other cellular insults. The ubiquitous presence of hsp70 in eukaryotic and prokaryotic cells, combined with its high degree of sequence homology and intrinsic immunogenicity, have prompted the suggestion that inappropriate immune reactivity to hsp70 might lead to pro-inflammatory responses and the development of autoimmune disease. Indeed, hsp70 has been shown to be a potent activator of innate immunity and aberrant expression of hsp70 in certain organs promotes immunopathology. However, studies also suggest that hsp70 might have immunotherapeutic potential, as hsp70 purified from malignant and virally infected cells can transfer and deliver antigenic peptides to antigen-presenting cells to elicit peptide-specific immunity and, in contrast to its reported pro-inflammatory effects, the administration of recombinant hsp70 can attenuate experimental autoimmune disease. This review focuses on the immunoregulatory capacity of hsp70 and its potential therapeutic value. [source] Emerging role of mitogen-activated protein kinases in peripheral neuropathiesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2007Guido Cavaletti Abstract Among the different families of intracellular molecules that can be modulated during cell damage and repair, mitogen-activated protein kinases (MAPKs) are particularly interesting because they are involved in several intracellular pathways activated by injury and regeneration signals. Despite most of the studies have been performed in non-neurological models, recently a causal role for MAPKs has been postulated in central nervous system disorders. However, also in some peripheral neuropathies, MAPK changes can occur and these modifications might be relevant in the pathogenesis of the damage as well as during regeneration and repair. In this review, the current knowledge on the role of MAPKs in peripheral neuropathies will be discussed. [source] | |||||||||||||