Recent findings have shown that, in addition to the genomic action of steroids, through intracellular receptors, short-time effects could be mediated binding membrane sites. In present study prostate cancer LNCaP cells, we report that dihydrotestosterone and non-internalizable analog testosterone-BSA increase rapidly release prostate-specific antigen (PSA) culture medium. Membrane testosterone sites were identified ligand on preparations, flow cytometry, confocal laser microscopy fluorescent...

The human prostate cancer cell line LNCaP bears functional membrane testosterone receptors, which modify the actin cytoskeleton and increase secretion of prostate-specific antigen (PSA) within minutes. Membrane steroid receptors are, indeed, a newly identified element action that is different from classical intracellular sites. In present work, using nonpermeable analog (testosterone-BSA), we investigated signaling pathway triggered by receptors' activation leads to reorganization. We report...

Nongenomic androgen actions imply mechanisms different from the classical intracellular receptor (iAR) activation. We have recently reported identification of a membrane (mAR) on LNCaP human prostate cancer cells, mediating testosterone signal transduction within minutes. In present study we provide evidence that activation mAR by nonpermeable, BSA-coupled results in 1) inhibition cell growth (with 50% inhibitory concentration 5.08 nM, similar to affinity for sites); 2) induction cells both...

The expression and function of the 8 distinct catalytic isoforms PI 3-kinase (PI3K) in nervous system are unknown. Whereas most PI3Ks have a broad tissue distribution, tyrosine kinase-linked p110δ isoform has previously been shown to be enriched leukocytes. Here we report that is also highly expressed system. Inactivation mice did not affect gross neuronal development but led an increased vulnerability dorsal root ganglia neurons exhibit growth cone collapse decreases axonal extension. Loss...

The family of p21-activated kinases (PAKs) have been implicated in the rearrangement actin cytoskeleton by acting downstream small GTPases Rac and Cdc42. Here we report that even though Cdc42/Rac1 or Akt are not activated, phosphatidylinositol-3 (PI-3) kinase activation induces PAK1 activity. Indeed, demonstrate PI-3 associates with N-terminal regulatory domain (amino acids 67–150) leading to activation. association binding-deficient PAK1(H83,86L) confirms involved kinase-PAK1 interaction....

The class IA isoforms of phosphoinositide 3-kinase (p110α, p110β and p110δ) often have non-redundant functions in a given cell type. However, for reasons that are unclear, the role specific PI3K isoform can vary between types. Here, we compare relative contributions primary immortalised macrophages. In macrophages stimulated with tyrosine kinase ligand colony-stimulating factor 1 (CSF1), all participate regulation Rac1, whereas p110δ selectively controls activities Akt, RhoA PTEN, addition...

Class IA PI3Ks consists of three isoforms the p110 catalytic subunit designated p110α, p110β, and p110δ which are encoded by separate genes. Gain-of-function mutations on PIK3CA gene encoding for p110α isoform have been detected in a wide variety human cancers whereas no somatic genes p110β or reported. Unlike ubiquitously expressed, is highly enriched leukocytes thus PI3K pathway has attracted more attention its involvement immune disorders. However, findings accumulated showing that plays...

Excessive pro-inflammatory cytokine production in the bone marrow has been associated with pathogenesis of myelodysplastic syndromes. We herein investigated involvement toll-like receptors and their endogenous ligands induction/maintenance inflammatory process patients evaluated expression monocytes (n=27) healthy controls (n=25) by flow-cytometry also assessed activation respective signaling using a real-time polymerase chain reaction-based array. measured high mobility group box-1 protein,...

Abstract Patient selection for PI3K-targeted solid cancer treatment was based on the PIK3CA/PTEN mutational status. However, it is increasingly clear that this not a good predictor of response breast cells to anti-proliferative effect PI3K inhibitors, indicating isoform(s) other than p110α may modulate sensitivity inhibition. Surprisingly, we found although no mutations in p110δ subunit have been detected thus far cancer, expression becomes gradually elevated during human progression from...

Class IA PI3K isoforms have divergent, nonredundant cell biological roles. In untransformed cells and tissues, p110a p110β are ubiquitously expressed, whereas p110δ expression is highly enriched in leukocytes. High levels of been documented some solid tumor lines, but the functional role unknown. This study aimed to elucidate link between elevated cancer. We report that breast prostate cancer contain leukocyte p110δ, activity dampens PTEN suppressor. Indeed, inactivation these led...

Abstract Genomic signaling mechanisms require a relatively long time to get into action and represent the main way through which steroid hormones affect target cells. In addition, steroids may rapidly activate cellular functions by non-genomic involving membrane sites. Understanding in depth molecular of represents an important frontier for developing new more selective pharmacologic tools endocrine therapies. present study, we report that membrane-impermeable testosterone-bovine serum...

Although the renal proximal tubular epithelial cells are targeted in a variety of inflammatory diseases kidney, signaling mechanism by which tumor necrosis factor (TNF)-α exerts its effects these remains unclear. Here, we report that TNF-α elicits antiapoptotic opossum kidney and this response is mediated via actin redistribution through novel mechanism. More specifically, show prevents apoptosis inhibiting activity caspase-3 effect depends on polymerization state nuclear factor-κB activity....

Opioids and somatostatin analogs have been implicated in the modulation of renal water handling, but whether their action is accomplished through central and/or peripheral mechanisms remains controversial. In different cell systems, on other hand, opioids inhibit proliferation. present study, we used an established line, derived from opossum kidney (OK) proximal tubules, order to characterize opioid receptors investigate tubular epithelial tissue. Our results show presence one class binding...

Opioids and somatostatin analogs have been implicated in the modulation of renal water handling, but whether their action is accomplished through central and/or peripheral mechanisms remains controversial. In different cell systems, on other hand, opioids inhibit proliferation. present study, we used an established line, derived from opossum kidney (OK) proximal tubules, order to characterize opioid receptors investigate tubular epithelial tissue. Our results show presence one class binding...

Opioids decrease cell proliferation in different systems including breast, prostate, lung, kidney, and intestine, through an interaction with opioid as well other membrane-receptor (somatostatin, cholinergic), unidentified mechanism. Recently, we have reported of taxol membrane sites (BBRC 235, 201–204, 1997), involvement opioids to the modification actin cytoskeleton renal OK cells (J Cell Biochem. [1998] 70:60–69), indicating a possible action effect. In present work, examined effect two...

We studied with biochemical and immunofluorescent techniques the interactions between actin microfilament tubulin microtubule cytoskeleton Na+/Pi co-transport in opossum kidney cells, a line proximal tubular characteristics. On brief (5 min) incubation of cells low (0.1 mM) concentration Pi, rapid F-actin depolymerization takes place, which fails to occur incubated under similar conditions 1 mM Pi. The disassembly microfilaments could be quantitatively expressed as 33% increase ratio...

Endometriosis is considered as a benign aseptic inflammatory disease, characterised by the presence of ectopic endometrium-like tissue. Its symptoms (mostly pain and infertility) are reported constant stressors. Corticotropin releasing hormone (CRH) urocortin (UCN) neuropeptides, strongly related to stress inflammation. The effects CRH UCN mediated through CRHR1 CRHR2 receptors which implicated in several reproductive functions acting components. However, involvement these molecules...

The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor protein is regulated by various mechanisms that are not fully understood. This includes regulation Tyr phosphorylation a mechanism remains elusive. Here, we show focal adhesion kinase (FAK) phosphorylates PTEN in vitro, cell-free systems cells. Furthermore, mass spectrometry, identified Tyr336 as being phosphorylated FAK increased activity, protein-lipid interaction, stability of PTEN. In cells, including...

Endometriosis is an inflammatory disease of women reproductive age featured by the presence ectopic endometrium and strongly related to infertility. Galectins, carbonhydrate-binding proteins, have been found pro- or anti-inflammatory roles in tract pathological conditions concerning Galectin-1, which expressed at decidua, plays a major role implantation trophoblast invasion. Also, neuropeptides, corticotropin releasing hormone (CRH) urocortin (UCN) their receptors are eutopic showing...