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Ceramide melanocyte

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https://www.readbyqxmd.com/read/29428730/targeting-sphingosine-kinase-2-by-abc294640-inhibits-human-skin-squamous-cell-carcinoma-cell-growth
#1
Jianbo Zhou, Jin Chen, Huanmiao Yu
The activity of ABC294640, a small-molecular sphingosine kinase 2 (SphK2) inhibitor, in human skin squamous cell carcinoma (SCC) cells was tested in this study. SphK2 mRNA and protein are expressed in established (A431 cheilocarcinoma cell line) and primary human skin SCC cells. ABC294640 dose-dependently inhibited survival, cell cycle progression and proliferation of skin SCC cells. Furthermore, ABC294640 induced caspase-3/-9 and apoptosis activation in skin SCC cells. The SphK2 inhibitor was however non-cytotoxic to SphK2-null skin melanocytes, keratinocytes and fibroblasts...
March 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28739255/wp1066-a-small-molecule-inhibitor-of-the-jak-stat3-pathway-inhibits-ceramide-glucosyltransferase-activity
#2
Hirotaka Tsurumaki, Hikaru Katano, Kousuke Sato, Ryou Imai, Satomi Niino, Yoshio Hirabayashi, Shinichi Ichikawa
WP1066 is a well-known inhibitor of the JAK/STAT3 signaling pathway. By a screen of known small molecule inhibitors of various enzymes and protein factors, we identified WP1066 as a ceramide glucosyltransferase inhibitor. Ceramide glucosyltransferase catalyzes the first glycosylation step during glycosphingolipid synthesis. We found that WP1066 inhibited the activity of ceramide glucosyltransferase with an IC50 of 7.2 μM, and that its action was independent of JAK/STAT3 pathway blockade. Moreover, the modes of inhibition of ceramide glucosyltransferase were uncompetitive with respect to both C6 -NBD-cermide and UDP-glucose...
September 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27631768/liposomal-c6-ceramide-activates-protein-phosphatase-1-to-inhibit-melanoma-cells
#3
Fangzhen Jiang, Kai Jin, Shenyu Huang, Qi Bao, Zheren Shao, Xueqing Hu, Juan Ye
Melanoma is one common skin cancer. In the present study, the potential anti-melanoma activity by a liposomal C6 ceramide was tested in vitro. We showed that the liposomal C6 (ceramide) was cytotoxic and anti-proliferative against a panel of human melanoma cell lines (SK-Mel2, WM-266.4 and A-375 and WM-115). In addition, liposomal C6 induced caspase-dependent apoptotic death in the melanoma cells. Reversely, its cytotoxicity was attenuated by several caspase inhibitors. Intriguingly, liposomal C6 was non-cytotoxic to B10BR mouse melanocytes and primary human melanocytes...
2016: PloS One
https://www.readbyqxmd.com/read/26553872/acid-ceramidase-in-melanoma-expression-localization-and-effects-of-pharmacological-inhibition
#4
Natalia Realini, Francesca Palese, Daniela Pizzirani, Silvia Pontis, Abdul Basit, Anders Bach, Anand Ganesan, Daniele Piomelli
Acid ceramidase (AC) is a lysosomal cysteine amidase that controls sphingolipid signaling by lowering the levels of ceramides and concomitantly increasing those of sphingosine and its bioactive metabolite, sphingosine 1-phosphate. In the present study, we evaluated the role of AC-regulated sphingolipid signaling in melanoma. We found that AC expression is markedly elevated in normal human melanocytes and proliferative melanoma cell lines, compared with other skin cells (keratinocytes and fibroblasts) and non-melanoma cancer cells...
January 29, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26028612/toxicity-of-oxidized-phosphatidylcholines-in-cultured-human-melanoma-cells
#5
Claudia Ramprecht, Hannah Jaritz, Ingo Streith, Elfriede Zenzmaier, Harald Köfeler, Rainer Hofmann-Wellenhof, Helmut Schaider, Albin Hermetter
The oxidized phospholipids (oxPL) 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) and 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) are generated from 1-palmitoyl-2-arachidonoyl-phosphatidylcholine under conditions of oxidative stress. These oxPL are components of oxidized low density lipoprotein. They are cytotoxic in cells of the arterial wall thus playing an important role in the development and progression of atherosclerosis. The toxic lipid effects include inflammation and under sustained exposure apoptosis...
July 2015: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/24937072/multifaceted-pathways-protect-human-skin-from-uv-radiation
#6
REVIEW
Vivek T Natarajan, Parul Ganju, Amrita Ramkumar, Ritika Grover, Rajesh S Gokhale
The recurrent interaction of skin with sunlight is an intrinsic constituent of human life, and exhibits both beneficial and detrimental effects. The apparent robust architectural framework of skin conceals remarkable mechanisms that operate at the interface between the surface and environment. In this Review, we discuss three distinct protective mechanisms and response pathways that safeguard skin from deleterious effects of ultraviolet (UV) radiation. The unique stratified epithelial architecture of human skin along with the antioxidant-response pathways constitutes the important defense mechanisms against UV radiation...
July 2014: Nature Chemical Biology
https://www.readbyqxmd.com/read/24732399/basis-for-enhanced-barrier-function-of-pigmented-skin
#7
Mao-Qiang Man, Tzu-Kai Lin, Juan L Santiago, Anna Celli, Lily Zhong, Zhi-Ming Huang, Truus Roelandt, Melanie Hupe, John P Sundberg, Kathleen A Silva, Debra Crumrine, Gemma Martin-Ezquerra, Carles Trullas, Richard Sun, Joan S Wakefield, Maria L Wei, Kenneth R Feingold, Theodora M Mauro, Peter M Elias
Humans with darkly pigmented skin display superior permeability barrier function in comparison with humans with lightly pigmented skin. The reduced pH of the stratum corneum (SC) of darkly pigmented skin could account for enhanced function, because acidifying lightly pigmented human SC resets barrier function to darkly pigmented levels. In SKH1 (nonpigmented) versus SKH2/J (pigmented) hairless mice, we evaluated how a pigment-dependent reduction in pH could influence epidermal barrier function. Permeability barrier homeostasis is enhanced in SKH2/J versus SKH1 mice, correlating with a reduced pH in the lower SC that colocalizes with the extrusion of melanin granules...
September 2014: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/24632809/overexpressed-pkc%C3%AE-downregulates-the-expression-of-pkc%C3%AE-in-b16f10-melanoma-induction-of-apoptosis-by-pkc%C3%AE-via-ceramide-generation
#8
Kuntal Halder, Sayantan Banerjee, Anamika Bose, Saikat Majumder, Subrata Majumdar
In the present study, we observed a marked variation in the expression of PKCα and PKCδ isotypes in B16F10 melanoma tumor cells compared to the normal melanocytes. Interestingly, the tumor instructed expression or genetically manipulated overexpression of PKCα isotype resulted in enhanced G1 to S transition. This in turn promoted cellular proliferation by activating PLD1 expression and subsequent AKT phosphorylation, which eventually resulted in suppressed ceramide generation and apoptosis. On the other hand, B16F10 melanoma tumors preferentially blocked the expression of PKCδ isotype, which otherwise could exhibit antagonistic effects on PKCα-PLD1-AKT signaling and rendered B16F10 cells more sensitive to apoptosis via generating ceramide and subsequently triggering caspase pathway...
2014: PloS One
https://www.readbyqxmd.com/read/23203344/ceramide-pc102-inhibits-melanin-synthesis-via-proteasomal-degradation-of-microphthalmia-associated-transcription-factor-and-tyrosinase
#9
Hyo-Soon Jeong, Hye-Ryung Choi, Hye-Young Yun, Kwang Jin Baek, Nyoun Soo Kwon, Kyoung-Chan Park, Dong-Seok Kim
A few types of ceramide are reported to decrease melanin synthesis. In the present study, we examined the effects of an artificial ceramide analog, PC102, on melanogenesis using a spontaneously immortalized melanocyte cell line (Mel-Ab). PC102 is currently used as a moisturizing additive in a variety of cosmetics. Our data showed that PC102 inhibited melanin production and tyrosinase activity in a dose-dependent manner, but did not directly affect tyrosinase activity. Microphthalmia-associated transcription factor (MITF), tyrosinase, and β-catenin protein levels decreased after 48 h of PC102 treatment...
March 2013: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/22236408/targeting-sphingosine-kinase-1-to-inhibit-melanoma
#10
SubbaRao V Madhunapantula, Jeremy Hengst, Raghavendra Gowda, Todd E Fox, Jong K Yun, Gavin P Robertson
Resistance to therapies develops rapidly for melanoma leading to more aggressive disease. Therefore, agents are needed that specifically inhibit proteins or pathways controlling the development of this disease, which can be combined, dependent on genes deregulated in a particular patient's tumors. This study shows that elevated sphingosine-1-phosphate (S-1-P) levels resulting from increased activity of sphingosine kinase-1 (SPHK1) occur in advanced melanomas. Targeting SPHK1 using siRNA decreased anchorage-dependent and -independent growth as well as sensitized melanoma cells to apoptosis-inducing agents...
March 2012: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/16691509/transcriptional-activation-of-tyrosinase-gene-by-human-placental-sphingolipid
#11
Bidisha Saha, Suman Kumar Singh, Chinmoy Sarkar, Shampa Mallick, Rabindranath Bera, Ranjan Bhadra
The sphingolipids, a class of complex bioactive lipids, are involved in diverse cellular functions such as proliferation, differentiation, and apoptosis as well as growth inhibition. Recently sphingosylphosphorylcholine (SPC), sphingosine-1-phosphate (S1P), and C2-ceramide (C2-Cer), sphingolipid containing acetic acid are emerging as melanogenic regulators. A bioactive sphingolipid (PSL) was isolated from hydroalcoholic extract of fresh term human placenta and it induced melanogenesis in an in vitro culture of mouse melanoma B16F10 cells...
May 2006: Glycoconjugate Journal
https://www.readbyqxmd.com/read/15881612/sphingosine-1-phosphate-is-involved-in-cytoprotective-actions-of-calcitriol-in-human-fibroblasts-and-enhances-the-intracellular-bcl-2-bax-rheostat
#12
B Sauer, H Gonska, M Manggau, D S Kim, C Schraut, M Schäfer-Korting, B Kleuser
Calcitriol is originally known to decrease proliferation rates of several carcinoma cells, partly via induction of apoptosis. On the other hand, the secosteroid is revealed to protect some cell types like thyrocytes, HL-60 cells and melanocytes against programmed cell death. Here we report that calcitriol despite its strong antiproliferative effect on human dermal fibroblasts did not induce apoptosis in these cells. In contrast, calcitriol possessed an antiapoptotic action in dermal fibroblasts. Thus, the ability of the apoptotic stimuli TNFalpha/actinomycin and C2-ceramides (C2-Cer) to induce programmed cell death was drastically diminished in the presence of calcitriol...
April 2005: Die Pharmazie
https://www.readbyqxmd.com/read/14572633/conditional-expression-of-exogenous-bcl-x-s-triggers-apoptosis-in-human-melanoma-cells-in-vitro-and-delays-growth-of-melanoma-xenografts
#13
Amir M Hossini, Jürgen Eberle, Lothar F Fecker, Constantin E Orfanos, Christoph C Geilen
The Bcl-2-related proteins Bcl-X(L) and Bcl-X(S) represent alternative splice products and exert opposite activities in the control of apoptosis, but their significance for melanoma is not yet clear. Applying the tetracycline-inducible expression system Tet-On, we found overexpression of Bcl-X(S) by itself sufficient to induce apoptosis in vitro in stably transfected human melanoma cell lines. Combination with proapoptotic agents such as etoposide, pamidronate, and ceramide resulted in additive proapoptotic effects, whereas Bcl-X(L) protected from apoptosis caused via CD95/Fas stimulation...
October 23, 2003: FEBS Letters
https://www.readbyqxmd.com/read/12354415/effects-of-c2-ceramide-on-the-malme-3m-melanoma-cell-line
#14
Won Suk Han, Jong Yeop Yoo, Sang Woong Youn, Dong Seok Kim, Kyoung Chan Park, Sook Young Kim, Kyu Han Kim
Ceramide is implicated in the regulation of various signaling pathways leading to proliferation, differentiation or apoptotic cell death, but there have been few investigations about the effects of ceramide on the cell growth and the melanogenesis of melanocytes. In the present study, we investigated the effects of cell-permeable ceramide on Malme-3M human melanoma cell line. MTT proliferation assay showed that C2-ceramide inhibited the growth of Malme-3M cells in a dose-dependent manner. Cell cycle analysis confirmed the inhibition of DNA synthesis by a reduction in the S phase and an increase in the G0/G1 phase...
October 2002: Journal of Dermatological Science
https://www.readbyqxmd.com/read/12174089/vitamin-d-and-systemic-cancer-is-this-relevant-to-malignant-melanoma
#15
REVIEW
J E Osborne, P E Hutchinson
1,25-dihydroxyvitamin D3[1,25(OH)2D3] is a well-known potent regulator of cell growth and differentiation and there is recent evidence of an effect on cell death, tumour invasion and angiogenesis, which makes it a candidate agent for cancer regulation. The classical synthetic pathway of 1,25(OH)2D3 involves 25- and 1 alpha-hydroxylation of vitamin D3, in the liver and kidney, respectively, of absorbed or skin-synthesized vitamin D3. There is recent focus on the importance in growth control of local metabolism of 1,25(OH)2D3, which is a function of local tissue synthetic hydroxylases and particularly the principal catabolizing enzyme, 24-hydroxylase...
August 2002: British Journal of Dermatology
https://www.readbyqxmd.com/read/12034359/delayed-erk-activation-by-ceramide-reduces-melanin-synthesis-in-human-melanocytes
#16
Dong-Seok Kim, Sook-Young Kim, Jin-Ho Chung, Kyu-Han Kim, Hee-Chul Eun, Kyoung-Chan Park
Sphingolipid metabolites regulate many aspects of cell growth and differentiation. However, the effects of sphingolipids on the growth and melanogenesis of human melanocytes are not known. In the present study, we investigated the effects of sphingolipid metabolites and the possible signalling pathways involved in human melanocytes. Our data show that C(2)-ceramide inhibits cell growth in a dose-dependent manner, whereas sphingosine-1-phosphate (SPP) has no effect. Moreover, we observed that the melanin content of the cells was significantly decreased by C(2)-ceramide...
September 2002: Cellular Signalling
https://www.readbyqxmd.com/read/11310790/ceramide-inhibits-cell-proliferation-through-akt-pkb-inactivation-and-decreases-melanin-synthesis-in-mel-ab-cells
#17
D S Kim, S Y Kim, S J Moon, J H Chung, K H Kim, K H Cho, K C Park
Ceramide is a bioactive sphingolipid that mediates a variety of cell functions. However, the effects of ceramide on cell growth and the melanogenesis of melanocytes are not known. In the present study, we investigated the actions of cell-permeable ceramide and its possible role in the signaling pathway of a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Our results show that C2-ceramide inhibits DNA synthesis in Mel-Ab cells and G361 human melanoma cells in a dose-dependent manner. Cell cycle analysis confirmed the inhibition of DNA synthesis by a reduction in the S phase...
April 2001: Pigment Cell Research
https://www.readbyqxmd.com/read/9743348/alpha-melanocyte-stimulating-hormone-inhibits-the-nuclear-transcription-factor-nf-kappa-b-activation-induced-by-various-inflammatory-agents
#18
S K Manna, B B Aggarwal
Alpha-melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide found mainly in the brain, pituitary, and circulation. It inhibits most forms of inflammation by a mechanism that is not known. As most types of inflammation require activation of NF-kappa B, we investigated the effect of alpha-MSH on the activation of this transcription factor by a wide variety of inflammatory stimuli. Electrophoretic mobility shift assay showed that alpha-MSH completely abolished TNF-mediated NF-kappa B activation in a dose- and time-dependent manner...
September 15, 1998: Journal of Immunology: Official Journal of the American Association of Immunologists
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