Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to examine the role of opioids on cell migration, chemotaxis, invasion, and adhesion, with an emphasis on whether the opioid growth factor (OGF, [Met(5)]-enkephalin) or the opioid antagonist naltrexone (NTX) impacts any or all of these processes. Drug concentrations of OGF and NTX known to depress or stimulate, respectively, cell proliferation and growth were analyzed. Three different human cancers (pancreatic, colon, and squamous cell carcinoma of the head and neck), represented by seven different cancer cell lines (PANC-1, MIA PaCa-2, BxPC-3, CAL-27, SCC-1, HCT-116, and HT-29), were evaluated. In addition, the influence of a variety of other natural and synthetic opioids on cell motility, invasion, and adhesion was assessed. Positive and negative controls were included for comparison. OGF and NTX at concentrations of 10(-4) to 10(-6)M, and dynorphin A1-8, beta-endorphin, endomorphin-1, endomorphin-2, leucine enkephalin, [D-Pen(2,5)]-enkephalin (DPDPE), [D-Ala(2), MePhe(4), Glycol(5)]-enkephalin (DAMGO), morphine, and U69,593 at concentrations of 10(-6)M, did not alter cell migration, chemotaxis, or invasion of any cancer cell line. OGF and NTX at a concentration of 10(-6)M, and incubation for 24 or 72h, did not change adhesion of these cancer cells to collagen I, collagen IV, fibronectin, laminin, or vitronectin. Moreover, all other opioids tested at 10(-6)M concentrations and for 24h had no effect on adhesion. These results indicate that the inhibitory or stimulatory actions of OGF and NTX, respectively, on cell replication and growth are independent of cell migration, chemotaxis, invasion, and adhesive properties. Moreover, a variety of other exogenous and endogenous opioids, many specific for the micro, delta, or kappa opioid receptors, also did not alter these biological processes, consonant with previous observations of a lack of effects of these compounds and their receptors on the biology of cancer cells.
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PMID:Opioids and migration, chemotaxis, invasion, and adhesion of human cancer cells. 1791 Aug 95

Meprin metalloproteinases have been implicated in the susceptibility to and progression of diabetic nephropathy and inflammatory bowel diseases. Our studies with experimental models of these diseases in mice are congruent with the conclusion that meprins modulate the inflammatory responses and tissue damage. To determine whether the mouse and human enzymes differ, recombinant forms of meprin A from the two species were compared with respect to structure, substrates and inhibitors. Human homo-oligomeric meprin A formed oligomers ranging from 950,000 to 1,500,000 Da vs. 900,000 Da for mouse meprin A. Human and mouse meprin A exhibited similar activity against azocasein, fibronectin, collagen IV, and peptides such as parathyroid hormone, ghrelin, and gastrin-releasing peptide. The human enzyme had lower activity against gelatin, bradykinin, alpha-melanocyte-stimulating hormone and neurotensin, and higher activity against secretin and orcokinin. Human meprin A showed a preference for acidic residues in the P1' position of the substrate, unlike mouse meprin A. Several metalloproteinase inhibitors had IC(50) values in the nanomolar range, but potency ranged from similar values to a difference of several orders of magnitude for meprins from the two species. This work provides valuable data to improve predictability for human systems based on meprin functions in mouse models.
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PMID:Human and mouse homo-oligomeric meprin A metalloendopeptidase: substrate and inhibitor specificities. 1797 9

Prematurity continues to be the leading cause of neonatal death and developmental disability, highlighting the importance of identifying potential predictors of prematurity as well as interventions that can be linked to the predictors. This review covers recent research on potential psychological, physiological, and biochemical predictors. Among the psychological stressors are depression, anxiety, difficult relationships, and lack of social support. Biochemical predictors include corticotropin-releasing hormone, cortisol, and fetal fibronectin. A program of research that links an intervention for prematurity with a predictor for prematurity, that is, massage therapy to reduce cortisol and, in turn, reduce prematurity, is then presented.
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PMID:Prematurity and potential predictors. 1820 83

The adrenal cortex undergoes constant dynamic structural changes, a key element in ensuring integrative functionality of the gland. Studies have shown that the cellular environment can modulate cell functions such as proliferation and steroid secretion. For example, 3-day treatment with angiotensin II promotes protein synthesis with a concomitant decrease in proliferation of glomerulosa cells, when cultured on fibronectin, but not on collagen IV or laminin. These effects involve close interaction between cytoskeleton-associated proteins and activation of p42/p44mapk and p38 MAPK pathways. On the other hand, adrenocorticotropin hormone (ACTH), which is clearly the most potent stimulus of fasciculata cells, induces specific modulation of targeted proteins, when cells are cultured on collagen IV, but not on fibronectin or laminin. In particular, ACTH treatment leads to increased expression of Seladin-1 and induces the relocalization of Seladin-1 from the cytoplasm to the nucleus, both in vivo and in culture conditions, in adult rats and in human fetal adrenal glands. As a whole, these results indicate that Seladin-1, together with collagen IV, is able to modulate ACTH responsiveness. Hence, Seladin-1 may participate in the regulation of steroidogenesis when localized in the cytoplasm, while conversely protecting cells against oxidative stress generated by intense ACTH stimulation when massively localized in the nucleus.
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PMID:From integrative signalling to metabolic disorders. 1846 84

1. Obesity is a metabolic disease of pandemic proportions largely arising from positive energy balance, a consequence of sedentary lifestyle, conditioned by environmental and genetic factors. Several central and peripheral neurohumoral factors (the major ones being the anorectic adipokines leptin and adiponecin and the orexigenic gut hormone ghrelin) acting on the anorectic (pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript) and orexigenic (neuropeptide Y and agouti gene-related protein) neurons regulate energy balance. These neurons, mainly in the arcuate nucleus of the hypothalamus, project to parts of the brain modulating functions such as wakefulness, autonomic function and learning. A tilt in the anorectic-orexigenic balance, perhaps determined genetically, leads to obesity. 2. Excess fat deposition requires space, created by adipocyte (hypertrophy and hyperplasia) and extracellular matrix (ECM) remodelling. This process is regulated by several factors, including several adipocyte-derived Matrix metalloproteinases and the adipokine cathepsin, which degrades fibronectin, a key ECM protein. Excess fat, also deposited in visceral organs, generates chronic low-grade inflammation that eventually triggers insulin resistance and the associated comorbidities of metabolic syndrome (hypertension, atherosclerosis, dyslipidaemia and diabetes mellitus). 3. The perivascular adipose tissue (PVAT) has conventionally been considered non-physiological structural tissue, but has recently been shown to serve a paracrine function, including the release of adipose-derived relaxant and contractile factors, akin to the role of the vascular endothelium. Thus, PVAT regulates vascular function in vivo and in vitro, contributing to the cardiovascular pathophysiology of the metabolic syndrome. Defining the mechanism of PVAT regulation of vascular reactivity requires more and better controlled investigations than currently seen in the literature.
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PMID:Obesity, metabolic syndrome, adipocytes and vascular function: A holistic viewpoint. 2108 97

Alpha-melanocyte stimulating hormone (alpha-MSH) is a proopiomelanocortin derivative and a multi-function neuropeptide, well know for its pigment-inducing capacity, inhibitory action on proinflammatory cytokines and chemoattractant cytokines, and suppressive action on collagen synthesis. Human Tenon's capsule fibroblasts (HTF) are the main effector cells in the initiation and mediation of wound healing and fibrotic scar formation after trabeculectomy. In this study the effects of alpha-MSH on proliferation of HTF stimulated by transforming growth factor beta1 (TGF-beta1), have been investigated and discussed. Fibroblasts were cultured in Dulbecco's modified Eagle's medium (DMEM) in the control group, and in DMEM with TGF-beta1 at concentration of 10(-12) M in the TGF-beta1 group, and DMEM with 10(-12) M TGF-beta1 and alpha-MSH ranging from 0, 10(-8) to 10(-4) M in the TGF-beta1/alpha-MSH groups. Cell proliferation was assessed 48 h later by the CellTiter 96 Aqueous One Solution Cell Proliferation Assay. After administration of TGF-beta1 at a concentration of 10(-12) M, or TGF-beta1 at 10(-12) M plus alpha-MSH at 10(-6) M, the mRNA level of type I (alpha1) collagen, fibronectin, TNF-alpha, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), MMP-1, MMP-2, TIMP-1, and TIMP-2 in HTF were analyzed using the real time reverse transcription polymerase chain reaction. Alpha-MSH demonstrated an inhibitory effect on the proliferation of HTF induced by TGF-beta1 in a dose-dependent manner, when the concentration was lower than 10(-5) M, and a suppressive effect on the mRNA expression of type I (alpha1) collagen, TNF-alpha, ICAM-1 and VCAM-1, which were up-regulated by TGF-beta1. Our results showed a reverse effect of alpha-MSH on the imbalance between MMPs and TIMPs compared with TGF-beta1. Based on all these results, we conclude that alpha-MSH could effectively suppress HTF proliferation and modulate correlative genes in collagen synthesis stimulated by TGF-beta1, which implies that alpha-MSH could be exploited in the treatment of conjunctival fibrotic scar disorder.
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PMID:Alpha-melanocyte stimulating hormone suppresses the proliferation of human tenon's capsule fibroblast proliferation induced by transforming growth factor beta 1. 2311 52


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