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)

Normal human cells, cells from nonmalignant proliferative lesions, and primary and metastatic tumor cells can be maintained in vitro and analyzed for requirements for growth in chemically defined media. The human melanocytic cell system with normal melanocytes, precursor nevus cells, and primary and metastatic melanoma cells has been extensively studied for the phenotypic properties of the cells, including their requirements for exogenous growth factors and other mitogens. In high calcium-containing W489 medium, normal melanocytes require four supplements: IGF-I (or insulin); bFGF, TPA, and alpha-MSH. Nevus cells are largely independent of bFGF. Depletion of TPA from medium is not as detrimental to nevus cells as it is to melanocytes, but the phorbol ester is still essential for maintenance of the typical nevic phenotype. Primary melanoma cells require at least one growth factor, IGF-I (or insulin), for continuous proliferation. On the other hand, metastatic cells of melanoma as well as of carcinomas of colon and rectum, bladder, ovary, and cervix are able to proliferate after a short adaptation period in medium depleted of any growth factors and other proteins. Doubling times of metastatic tumor cells in protein-free medium are only 30-60% longer than in FCS-containing medium. The growth autonomy of human tumor cells is apparently due to the endogenous production of growth factors. Likely candidates for autocrine growth stimulation of human tumor cells are TGF-alpha, TGF-beta, and PDGF. Melanoma and colorectal carcinoma cells express functional EGF/TGF-alpha receptors, and produce TGF-alpha, indicating that this growth factor is produced for autocrine stimulation. In addition to the use of anti-growth factor antibodies, other strategies for the inhibition of autocrine growth stimulation include mAbs to growth factor receptors, soluble receptors, receptor-mimicking antiidiotype antibodies, and active immunization against growth factors. Whether any of these therapeutic approaches is clinically feasible will need to be determined in extensive preclinical investigations.
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PMID:Growth-regulatory factors for normal, premalignant, and malignant human cells in vitro. 240 78

Melanocyte cultures were established and maintained routinely in Ham's F-10 medium containing 12-O-tetradecanoyl-phorbol-13-acetate (TPA), isobutylmethylxanthine (IBMX), cholera toxin (CT) and fetal calf serum (FCS). Three serum substitutes (Ultroser-G, Nutridoma-Hu and Nutricyte-H) were tested in order to obtain a medium without FCS having a more constant composition. Melanocyte proliferation was examined in long-term culture experiments by in situ cell counts at different periods of time. Only with Ultroser-G (1-2%) was the proliferation of melanocytes maintained without both FCS and CT, whereas the addition of the other two serum substitutes resulted in stabilization of melanocyte densities in the cultures up to 28 days. In the medium containing 1% Ultroser-G and IBMX without TPA minimal or no increases in melanocyte density were found. Addition of basic fibroblast growth factor (bFGF, 1 ng/ml) to the medium without TPA resulted in a partial restimulation of growth in different experiments. In this system with 1% Ultroser-G and 1 ng/ml bFGF, IBMX could also be replaced by other factors (dbcAMP, LTC4 and a purified form of alpha-melanocyte stimulating hormone). The culture medium with 1% Ultroser-G containing TPA and IBMX is now used for routine melanocyte culture. In this medium TPA/IBMX can easily be replaced by bFGF/dbcAMP with optimal growth stimulation. The combination bFGF/alpha-MSH and other more physiological stimulators offers an alternative to study responses of melanocytes in culture with respect to proliferation, metabolism, and phenotype.
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PMID:Stimulation of cultured melanocytes in medium containing a serum substitute: Ultroser-G. 754 Jul 55

We have successfully established normal neonatal and adult human melanocyte cultures in a growth medium containing the physiologic mitogens basic fibroblast growth factor (bFGF; 0.6 ng/ml), endothelin-1 (endo-1; 10 nM), and alpha-melanocyte stimulating hormone (alpha-MSH; 10 nM). The latter two factors replaced the commonly used mitogens 12-O-tetradecanoylphorbol 13-acetate (TPA) and bovine pituitary extract (BPE), respectively. Basic FGF alone maintained the viability but did not induce the proliferation of melanocytes. The addition of endo-1 to the bFGF-containing medium resulted in reduction of tyrosinase activity without enhancement of proliferation. However, the addition of alpha-MSH to the bFGF-containing medium potentiated melanocyte proliferation and tyrosinase activity. The concomitant addition of endo-1, alpha-MSH, and bFGF significantly increased the entry of melanocytes into S phase and potentiated their proliferation. Melanocytes maintained under these conditions had the same tyrosinase activity as those maintained in a medium containing alpha-MSH and bFGF. The signal transduction pathway induced by either endo-1 or bFGF, but not alpha-MSH, includes the activation of the mitogen-activated (MAP) kinase pathway. The addition of both endo-1 and bFGF had more than an additive effect on the MAP kinase extracellular signal-regulated kinase 2 (ERK2). This effect was further increased by the addition of alpha-MSH to these two growth factors. In summary, we have devised a growth medium for human melanocytes based on the use of physiologic mitogens that substituted for routinely used artificial and undefined growth factors. The resulting cultures should be desirable for clinical uses and permissive for the expression of in vivo relevant responses to regulatory factors.
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PMID:Long-term proliferation of human melanocytes is supported by the physiologic mitogens alpha-melanotropin, endothelin-1, and basic fibroblast growth factor. 769 46

Work in the past 8 years, particularly in the past 1-2 years, has greatly expanded our understanding of the mechanisms by which ultraviolet irradiation stimulates melanogenesis in the skin. A direct effect of UV photons on DNA results in up-regulation of the gene for tyrosinase, the rate-limiting enzyme in melanin synthesis, as well as an increase in cell surface expression of receptors for at least one of the several known keratinocyte-derived melanogenic factors, MSH. Direct effects of UV on melanocyte membranes, releasing DAG and arachidonic acid, may also play a role in the tanning response. Diacylglycerol may activate PKC-beta, which in turn phosphorylates and activates tyrosinase protein; the pathways by which products of other inflammatory mediator cascades may act on melanogenesis are unknown. The tanning response also relies heavily on UV-stimulated increased production and release of numerous keratinocyte-derived factors including bFGF, NGF, endothelin-1 and the POMC-derived peptides MSH, ACTH, beta-LPH and beta-endorphin. These factors variably induce melanocyte mitosis, increase melanogenesis, enhance dendricity and prevent apoptotic cell death following the UV injury. Thus, events within the epidermal melanin unit conspire to maintain or increase melanocyte number, increase melanin pigment throughout the epidermis. Overall, ultraviolet-induced melanogenesis may be one part of a eukaryotic SOS response to damaging ultraviolet irradiation that has evolved over time to provide a protective tan in skin at risk of further injury from sun exposure. These recent insights into the mechanisms underlying ultraviolet-induced melanogenesis offer the opportunity for novel therapeutic approaches to minimizing acute and chronic photodamage in human skin.
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PMID:Mechanisms of ultraviolet light-induced pigmentation. 857 60

Pulses (up to 2 h) of the adrenocorticotropic hormone (ACTH) rapidly activate p42 and p44 MAPK (5 min), induce the c-Fos protein (1 h, 80% of cells) and stimulate entry of mouse Y-1 adrenocortical cells into the S phase of the cell cycle. This set of sequential events is also triggered in Y-1 cells by bFGF, and reflects a mitogenic response to ACTH. We report here that 90% inhibition of c-fos mRNA translation with a c-fos antisense oligodeoxynucleotide completely blocks the entry of Y1 cells into S phase stimulated by pulses of ACTH. These results indicate that c-Fos protein is an intracellular mediator of the mitogenic response to ACTH.
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PMID:c-Fos protein is a mediator in mitogenic response to ACTH. 988 18

More than 150 genes have been identified that affect skin color either directly or indirectly, and we review current understanding of physiological factors that regulate skin pigmentation. We focus on melanosome biogenesis, transport and transfer, melanogenic regulators in melanocytes, and factors derived from keratinocytes, fibroblasts, endothelial cells, hormones, inflammatory cells, and nerves. Enzymatic components of melanosomes include tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase, which depend on the functions of OA1, P, MATP, ATP7A, and BLOC-1 to synthesize eumelanins and pheomelanins. The main structural component of melanosomes is Pmel17/gp100/Silv, whose sorting involves adaptor protein 1A (AP1A), AP1B, AP2, and spectrin, as well as a chaperone-like component, MART-1. During their maturation, melanosomes move from the perinuclear area toward the plasma membrane. Microtubules, dynein, kinesin, actin filaments, Rab27a, melanophilin, myosin Va, and Slp2-a are involved in melanosome transport. Foxn1 and p53 up-regulate skin pigmentation via bFGF and POMC derivatives including alpha-MSH and ACTH, respectively. Other critical factors that affect skin pigmentation include MC1R, CREB, ASP, MITF, PAX3, SOX9/10, LEF-1/TCF, PAR-2, DKK1, SCF, HGF, GM-CSF, endothelin-1, prostaglandins, leukotrienes, thromboxanes, neurotrophins, and neuropeptides. UV radiation up-regulates most factors that increase melanogenesis. Further studies will elucidate the currently unknown functions of many other pigment genes/proteins. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.
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PMID:Physiological factors that regulate skin pigmentation. 1944 48