Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production of pigment by melanocytic cells of the skin involves a series of enzymatic reactions that take place in specialized organelles called melanosomes. Melan-A/MART-1 is a melanocytic transmembrane protein with no enzymatic activity that accumulates in vesicles at the trans side of the Golgi and in melanosomes. We show here that, in melanoma cells, Melan-A associates with two homologous to E6-AP C-terminus (HECT)-E3 ubiquitin ligases, NEDD4 and Itch, and is ubiquitylated. Both NEDD4 and Itch participate in the degradation of Melan-A. A mutant Melan-A lacking ubiquitin-acceptor residues displays increased half-life and, in pigmented cells, accumulates in melanosomes. These results suggest that ubiquitylation regulates the lysosomal sorting and degradation of Melan-A/MART-1 from melanosomes in melanocytic cells.
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PMID:Ubiquitylation of a melanosomal protein by HECT-E3 ligases serves as sorting signal for lysosomal degradation. 1570 12

Little is known about children's ability to assess itch. The present paper aimed to investigate the discriminative capacity of two itch rating scales in children. Sixty healthy children, 4 to 12 years of age, participated. Itch was provoked with three histamine concentrations (0.1, 1.0, and 10 mg/ml). Physiologic saline was the negative control. The test solutions were pricked with a lancet into the skin of the lower arms in random order under coded conditions. The overall itch intensity for each skin prick was rated with a 100-mm visual analog scale and a four-stepped verbal rating scale (none, mild, moderate, and severe itch). In addition, the itch duration and flare response were recorded. A significant dose-response relationship was shown for the itch duration and itch intensity as rated with both scales. This was also true for the flare response, indicating a correct skin prick technique. However, children 4 to 5 years of age rated the itch intensity (both scales) less well than those aged 6 to 12 years. The younger age group discriminated between saline and histamine, but not between the different histamine concentrations. In conclusion, children aged 6 to 12 years were able to discriminate between different itch stimulus strengths in a dose-dependent way with a 100-mm visual analog scale and a four-stepped verbal rating scale, indicating the validity of these scales for measurement of experimental itch in children 6 years or older.
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PMID:Children's rating of itch: an experimental study. 1580 94

Itch in the elderly presents a diagnostic and therapeutic challenge. A thorough history, review of systems, and physical examination are critical to determining its cause. Examination of the skin may be misleading. There are frequently only secondary lesions, eczematous changes, lichenification, and excoriation, which may be misdiagnosed as a primary dermatitis. Xerosis may be the cause, but it is sometimes merely coincidental. If primary lesions are present, a skin biopsy can enable a diagnosis to be made. Systemic causes of itch, such as cholestasis, uremia, hyperthyroidism, medications, or lymphoma, must be considered. If the cause remains elusive, idiopathic itching of the elderly or so-called "senile pruritus" may be considered. However, we propose to discard the term "senile pruritus", which can be offensive and frightening. We propose to replace it with "Willan's itch". Robert Willan (1757-1812) is honored as one of the founders of modern dermatology thanks to his book, On Cutaneous Diseases, and its morphological approach to skin disease. He was probably the first to give a good clinical description of itching in the elderly. The diagnosis of Willan's itch should be reserved for generalized pruritus in the absence of xerosis or other recognizable cause. The pathophysiology of this form of pruritus is poorly understood, but it is likely that age-related changes of the skin, cutaneous nerves, and other parts of the nervous system play a role. Anecdotal and limited data suggest that gabapentin, cutaneous field stimulation, serotonin antagonists, and ultraviolet B phototherapy may attenuate itch in some of these patients.
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PMID:Willan's itch and other causes of pruritus in the elderly. 1581 Oct 75

p73, a homologue to the tumor suppressor gene p53, is involved in tumorigenesis, though its specific role remains unclear. The gene has two distinct promoters which allow the formation of two protein isoforms with opposite effects: full-length transactivating (TA) p73 shows pro-apoptotic effects, while the shorter DeltaNp73, which lacks the N-terminal transactivating domain, has an evident anti-apoptotic function. Unlike p53, the p73 gene is rarely mutated in human cancers. However, alterations in the relative levels of TA and DeltaNp73 have been shown to correlate with prognosis in several human cancers, suggesting that the fine regulation of these two isoforms is of pivotal importance in controlling proliferation and cell death. Much effort is currently focused on the elucidation of the mechanisms that differentially control TA and DeltaNp73 activity and protein stability, a process complicated by the finding that both proteins are regulated by a similar suite of complex post-translational modifications that include ubiquitination, sequential phosphorylation, prolyl-isomerization, recruitment into the PML-nuclear body (PML-NB), and acetylation. Here we shall consider the main regulatory partners of p73, with particular attention to the recently discovered Itch- and Nedd8-mediated degradation pathways, along with the emerging roles of PML, p38 MAP kinase, Pin1, and p300 in p73 transcriptional activation, and possible mechanisms for the differential regulation of the TAp73 and DeltaNp73 isoforms.
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PMID:Regulation of the p73 protein stability and degradation. 1586 26

The function of p73, a transcription factor belonging to the p53 family, is finely regulated by its steady-state protein stability. p73 protein degradation/stabilization can be regulated by mechanisms in part dependent on the ubiquitin proteasome system (UPS): (i) Itch/NEDD4-like UPS degradation, (ii) NEDD8 UPS degradation, and (iii) NQO1 20S proteasome-dependent (but ubiquitin-independent) breakdown. Here, we show that, in vitro, Calpain I can cleave p73 at two distinct sites: the first proline-rich region and within the oligomerization domain. Consequently, different p73 isoforms can be degraded by calpains, i.e., both N-terminal isoforms (TAp73 and DeltaNp73) as well as the C-terminal isoforms (alpha, beta, gamma, delta). Moreover, overexpression of the specific endogenous calpain inhibitor, calpastatin, in cultured cells increased the steady-state p73 level. This suggests that calpains may play a physiological role in the regulation of p73 protein stability.
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PMID:Calpain cleavage regulates the protein stability of p73. 1597 58

In lymphocytes, integration of Ca2+ and other signalling pathways results in productive activation, while unopposed Ca2+ signalling leads to decreased responsiveness to subsequent stimulation (anergy). The Ca(2+)-regulated transcription factor NFAT has an integral role in both aspects of lymphocyte function. NFAT cooperates with the transcription factor AP-1 (Fos/Jun) to up-regulate genes involved in productive activation of lymphocytes. However, in the absence of AP-1, NFAT imposes an opposing genetic programme that leads to lymphocyte anergy. Anergy is implemented at least partly through proteolytic degradation of the key signalling proteins PKCtheta and PLCgamma1. Sustained Ca(2+)-calcineurin signalling increases mRNA and protein levels of the E3 ubiquitin ligases Itch, CblB and Grail and induces expression of Tsg1O1, the ubiquitin-binding component of the ESCRT1 endosomal sorting complex. Subsequent stimulation or homotypic cell adhesion promotes membrane translocation of Itch and the related protein Nedd4, resulting in PKCtheta and PLCgamma1 degradation. T cells from Itch- and CblB-deficient mice are resistant to anergy induction. Anergic T cells show impaired calcium mobilization after TCR triggering and are unable to maintain a mature immunological synapse. Thus Ca(2+)-calcineurin-NFAT signalling links gene transcription to a multi-step programme that leads to impaired signal transduction in anergic T cells.
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PMID:A molecular dissection of lymphocyte unresponsiveness induced by sustained calcium signalling. 1599 6

To our knowledge there are no studies evaluating the prevalence and characteristics of itch, pain, and burning sensation among patients with mild to moderate chronic venous insufficiency or assessing the impact of these symptoms on quality of life. In this report 100 patients met the inclusion criteria. Patients who suffered from itch were also assessed with the use of a validated questionnaire and a modified Skindex-16 questionnaire. We found that the prevalence of itch was 66%. Concomitant itch and burning sensation as well as itch and pain were noted in 47% and 44% of the patients, respectively. No correlation was noted between the severity of these symptoms and the degree of venous insufficiency. Itch had a negative impact on quality of life. A limitation of this study is that the participants, who were primarily hospital employees, are more likely to develop these symptoms. Therefore this study does not reflect the true prevalence of these symptoms in the general population. This study found that itch, pain, and burning sensation are common symptoms of mild to moderate chronic venous insufficiency with a significant impact on quality of life.
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PMID:Itch, pain, and burning sensation are common symptoms in mild to moderate chronic venous insufficiency with an impact on quality of life. 1611 63

Itch is known to be a sensation that provokes a desire to scratch. It is a bio-warning sensation, which serves to detect and remove parasites and irritants in the superficial layers of the skin and the mucous membrane. The mechanisms of itch are not simple. It is mediated by mast cells and keratinocytes, which each produce and release a few itch mediators. Alterations in the distribution of primary afferent fibers in the epidermis are also involved in itch. Agents that have a wide spectrum of inhibitory action on mast cells, keratinocytes and primary afferents may be needed to effectively suppress itch.
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PMID:[Diverse mechanisms of itch]. 1619 Mar 69

A novel mode of crosstalk between the EGFR-Ras-MAPK and LIN-12/Notch pathways occurs during the patterning of a row of vulval precursor cells (VPCs) in Caenorhabditis elegans: activation of the EGFR-Ras-MAPK pathway in the central VPC promotes endocytosis and degradation of LIN-12 protein. LIN-12 downregulation in the central VPC is a prerequisite for the activity of the lateral signal, which activates LIN-12 in neighboring VPCs. Here we characterize cis-acting targeting sequences in the LIN-12 intracellular domain and find that in addition to a di-leucine motif, serine/threonine residues are important for internalization and lysine residues are important for post-internalization trafficking and degradation. We also identify two trans-acting factors that are required for post-internalization trafficking and degradation: ALX-1, a homolog of yeast Bro1p and mammalian Alix and the WWP-1/Su(dx)/Itch ubiquitin ligase. By examining the effects of mutated forms of LIN-12 and reduced wwp-1 or alx-1 activity on subcellular localization and activity of LIN-12, we provide evidence that the lateral signal-inhibiting activity of LIN-12 resides in the extracellular domain and occurs at the apical surface of the VPCs.
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PMID:LIN-12/Notch trafficking and regulation of DSL ligand activity during vulval induction in Caenorhabditis elegans. 1623 69

Itch and pruritus are two terms for the same thing. In this essay I will argue that casting about for a distinction between them creates only confusion. Once that matter is settled, it is still necessary to come up with a clinical classification for itches of different types. No system yet proposed, including the one that will be suggested here, is perfect.
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PMID:Itch and pruritus: what are they, and how should itches be classified? 1629 99


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