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Applying the basic knowledge about regulation of pigmentation towards development of strategies for cutaneous hypopigmentation

  • Abdel-Malek, Zalfa A.
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.28 no.3
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    • pp.7-39
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    • 2002
  • The extensive variation in human cutaneous pigmentation is mainly due to differences in the rate of melanin synthesis by epidermal melanocytes, the relative amounts of eumelanin and pheomelanin synthesized, and the manner and rate of transfer of melanosomes from melanocytes to keratinocytes. Pigmentation is a complex trait that is regulated genetically and environmentally. One gene that has been receiving a lot of attention is the gene for the melanocortin 1 receptor The extensive polymorphism of this gene in human populations suggests its significance in the diversity of pigmentation. Exposure to solar ultraviolet radiation (UV) results in increased synthesis of a variety of growth factors, cytokines and hormones, and in modulation of their receptors in the epidermis. Knowledge about the regulation of pigmentation has led to strategies for clinical treatment of hyperpigmented skin lesions. Three main strategies are: 1) the use of chemicals that interfere with the melanin synthetic pathway, 2) the design of peptides or peptide-mimetics based on the structure of hormones that regulate eumelanin synthesis, and 3) the use of agents that reduce melanosome transfer from melanocytes to keratinocytes. All three strategies are expected to induce hypopigmentation, by inhibiting total melanin synthesis, eumelanin production, or the epidermal melanin unit, respectively.

Effect on the Inhibition of DNA-PK in Breast Cancer Cell lines(MDA-465 and MDA-468) with DNA-PKcs Binding Domain Synthetic Peptide of Ku80 (Ku80의 DNA-PKcs 결합부위 합성 Peptide 투여에 의한 유방암세포의 DNA-dependent protein kinase 억제 효과)

  • 김충희;김태숙;문양수;정장용;강정부;김종수;강명곤;박희성
    • Journal of Veterinary Clinics
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    • v.21 no.3
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    • pp.253-258
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    • 2004
  • DNA double-strand break (DSB) is a serious treat for the cells including mutations, chromosome rearrangements, and even cell death if not repaired or misrepaired. Ku heterodimer regulatory DNA binding subunits (Ku70/Ku80) bound to double strand DNA breaks are able to interact with 470-kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and the interaction is essential for DNA-dependent protein kinase (DNA-PK) activity. The Ku80 mutants were designed to bind Ku70 but not DNA end binding activity and the peptides were treated in breast cancer cells for co-therapy strategy to see whether the targeted inhibition of DNA-dependent protein kinase (DNA-PK) activity sensitized breast cancer cells to ionizing irradiation or chemotherapy drug to develop a treatment of breast tumors by targeting proteins involved in damage-signaling pathway and/or DNA repair. We designed domains of Ku80 mutants, 26 residues of amino acids (HN-26) as a control peptide or 38 (HNI-38) residues of amino acids which contain domains of the membrane-translocation hydrophobic signal sequence and the nuclear localization sequence, but HNI-38 has additional twelve residues of peptide inhibitor region. We observed that the synthesized peptide (HNI-38) prevented DNA-PKcs from binding to Ku70/Ku80, resulting in inactivation of DNA-PK complex activity in breast cancer cells (MDA-465 and MDA-468). Consequently, the peptide treated cells exhibited poor to no DNA repair, and became highly sensitive to irradiation or chemotherapy drugs. The growth of breast cancer cells was also inhibited. These results demonstrate the possibility of synthetic peptide to apply breast cancer therapy to induce apoptosis of cancer cells.

Forward Gene Mutation Assay of Seven Benzophenone-type UV Filters using L5178Y Mouse Lymphoma Cell

  • Jeon, Hee-Kyung;Sarma, Sailendra Nath;Kim, Youn-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.3 no.1
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    • pp.23-30
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    • 2007
  • The effects of high energy short wave solar radiation on human skin have received much publicity as the major cause of accelerated skin ageing and of skin cancers. To meet public demand, the cosmetic industry has developed sun protection factor products, which contain a variety of so-called "UV filters", among others benzophenone (BP) and its metabolites are the widely used UV filters. UV filters are also used to prevent UV light from damaging scents and colors in a variety of cosmetics products and to protect of plastic products against light-induced degradation. There are many variants of BP in use. In this respect, to regulate and to evaluate the hazardous effect of BP-type UV filters will be important to environment and human health. The genotoxicity of 7 BP-type UV filters was evaluated in L5178Y $(tk^{+/-})$ mouse lymphoma cells in vitro. BP, benzhydrol, 4-hydroxybenzophenone 2-hydroxy-4-methoxybenzophenone and 2, 4-dihydroxybenzophenone did not induce significant mutation frequencies both in the presence and absence of metabolic activation system. 2, 2'-Dihydroxy-4-methoxybenzophenone appeared the positive results at the highest dose, i.e. 120.4 ${\mu}g/mL$ only in the absence of metabolic activation system. And also, 2, 3, 4-trihydroxybenzophenone revealed a significant increase of mutation frequencies in the range of 138.1-207.2 ${\mu}g/mL$ in the absence of metabolic activation system and 118.3-354.8 ${\mu}g/mL$ in the presence of metabolic activation system. Through the results of MLA with 7 BP-type UV filters in L5178Y cells in vitro, we may provide the important clues on the genotoxic potentials of these BP-type UV filters.

A Study on the Behaviour of Smoke Spread Caused by Vehicle Fire in a Road Tunnel (터널 내 차량 화재에 따른 연기 확산 거동에 관한 연구)

  • Yoon, Yong-Kyun;Ju, Eun-Hye
    • Tunnel and Underground Space
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    • v.22 no.5
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    • pp.365-372
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    • 2012
  • This paper aims to evaluate the effects that presence, installation number and capacity of ventilation vent and presence of multiple fire sources have on the behaviour of smoke temperature induced by vehicle fire in road tunnel. Six types of scenarios were assumed and FDS was ran to simulate them. As the number of ventilation vents increases, the smoke temperature are calculated to be reduced, but it is shown that effects exerted by two ventilation vents are almost similar to ones by three ventilation vents. Capacity of ventilation vent has a greater impact on the reduction of smoke temperature than installation number of ventilation vents. Smoke temperatures computed for all scenarios except for scenario No. 1 (without ventilation vent) and scenario No. 6 (with multiple fire sources) above fire source are analyzed to be under $400^{\circ}C$ and it means that the radiation of smoke layer above fire source doesn't induce the ignition of materials around fire source.

Reduction of Photodamage by TopicaI Application of a Novel Anti-Wrinkle Agent Containing Growth Factors

  • Kim, Ju-Mi;Ahn, Gook-Jun;Sohn, Young-Sung;Kang, Kyung-Koo;Ahn, Byoung-Ok;Lee, Jung-Hwan;Kim, Byung-Moon;Kwon, Jong-Won;Kim, Won-Bae
    • Biomolecules & Therapeutics
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    • v.12 no.3
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    • pp.157-164
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    • 2004
  • DA-3711 is a novel anti-wrinkle agent containing growth factors derived from culture medium of artificial human skin. Photoprotective effect by DA-3711 against chronic UVB (ultraviolet B)-induced skin damage was investigated in hairless mice model. Methods: After hairless mice were irradiated to induce photodamage for 8 weeks with UVB, grouped mice were treated topically once a day with lotion base, DA-3711 (30% or l5%), Cylasphere retinol$^{\circed{R}}$ (2500 I.U.), NouriCel$^{\circed{R}}$ along with concomitant exposure to UVB for further 8 weeks. Then mice were sacrificed to assess photodamage-protective effect by replica analysis, biochemistry and histology. DA-3711 of 30% lotion significantly reduced UVB radiation-induced wrinkling, histological alterations and increased collagen contents. Whereas DA-3711 of l5% lotion and NouriCel$^{\circed{R}}$ treatment showed a partial protective effect on skin wrinkle, epidermal and dermal thickness, and collagen content, Cylasphere retinol$^{\circed{R}}$ showed no protective effects. These results demonstrate that topical application of DA-3711 can alleviate UVB-induced photodamage and potentially be used for reduction of UVB-induced photodamage.

Increased Expression of FosB through Reactive Oxygen Species Accumulation Functions as Pro-Apoptotic Protein in Piperlongumine Treated MCF7 Breast Cancer Cells

  • Park, Jin-Ah;Na, Han-Heom;Jin, Hyeon-Ok;Kim, Keun-Cheol
    • Molecules and Cells
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    • v.42 no.12
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    • pp.884-892
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    • 2019
  • Piperlongumine (PL), a natural alkaloid compound isolated from long pepper (Piper longum), can selectively kill cancer cells, but not normal cells, by accumulation of reactive oxygen species (ROS). The objective of this study was to investigate functional roles of expression of SETDB1 and FosB during PL treatment in MCF7 breast cancer cells. PL downregulates SETDB1 expression, and decreased SETDB1 expression enhanced caspase 9 dependent-PARP cleavage during PL-induced cell death. PL treatment generated ROS. ROS inhibitor NAC (N-acetyl cysteine) recovered SETDB1 expression decreased by PL. Decreased SETDB1 expression induced transcriptional activity of FosB during PL treatment. PARP cleavage and positive annexin V level were increased during PL treatment with FosB overexpression whereas PARP cleavage and positive annexin V level were decreased during PL treatment with siFosB transfection, implying that FosB might be a pro-apoptotic protein for induction of cell death in PL-treated MCF7 breast cancer cells. PL induced cell death in A549 lung cancer cells, but molecular changes involved in the induction of these cell deaths might be different. These results suggest that SETDB1 mediated FosB expression may induce cell death in PL-treated MCF7 breast cancer cells.

One-dimensionally Ordered Array of Co and Fe Nanoclusters on Carburized-W(110) via Template Assisted Self-Assembly

  • Kim, Ji-Hyun;Yang, Serlun;Kim, Jae-Sung;Lukashev, Pavel;Rojas, Geoffrey;Enders, Axel;Sessi, Violetta;Honolka, Jan
    • Proceedings of the Korean Vacuum Society Conference
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    • 2012.02a
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    • pp.135-136
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    • 2012
  • Carbon atoms near the surface of W(110) induce reconstructions such as $R(15{\times}12)$ -C/W(110) which consists of two characteristic parts, one square shaped and bright protrusion and two smaller ones. In the atomic resolution STM image, the bigger protrusion shows the periodicities of clean W(110), indicating that it is almost carbon poor region. The smaller protrusion contains hexagonal carbide surface layer of ${\alpha}$-W2C on W(110). Employing this carburized W(110) as templates, we grow Co and Fe clusters of less than ten atoms. Due to the selectivity of bonding sites, growth of larger cluster is highly unfavorable for Co and the size of clusters is very uniform. Since Co atoms prefer to sit on the bigger protrusion rather than smaller one, Co cluster can be arranged one-dimensionally in $R(15{\times}12)$-C/W(110) with quite uniform size distribution. However, Fe clusters sit on both sites without favored site, but still with uniform size distribution. On the other hand, Fe clusters can be grown with quasi one-dimensional order in $R(15{\times}3)$-C/W(110), which consists of only smaller protrusions. We investigate the magnetic properties of the ordered nano-sized clusters. Experiments using XMCD reveals little magnetic moment of Co cluster on $R(15{\times}12)$-C/W(110). This observation is consistent with the predictions of our first principles calculations that small Co clusters can be nonmagnetic or antiferromagnetic with low mean magnetic moment per atom.

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Effect of Microalgal Extracts of Tetraselmis suecica against UVB-Induced Photoaging in Human Skin Fibroblasts

  • Jo, Wol Soon;Yang, Kwang Mo;Park, Hee Sung;Kim, Gi Yong;Nam, Byung Hyouk;Jeong, Min Ho;Choi, Yoo Jin
    • Toxicological Research
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    • v.28 no.4
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    • pp.241-248
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    • 2012
  • Exposure of cells to ultraviolet B (UVB) radiation can induce production of free radicals and reactive oxygen species (ROS), which damage cellular components. In addition, these agents can stimulate the expression of matrix metalloproteinase (MMP) and decrease collagen synthesis in human skin cells. In this study, we examined the anti-photoaging effects of extracts of Tetraselmis suecica (W-TS). W-TS showed the strongest scavenging activity against 2,2-difenyl-1-picrylhydrazyl (DPPH) and peroxyl radicals, followed by superoxide anions from the xanthine/xanthine oxidase system. We observed that the levels of both intracellular ROS and lipid peroxidation significantly increased in UVB-irradiated human skin fibroblast cells. Furthermore, the activities of enzymatic antioxidants (e.g., superoxide dismutase) and the levels of non-enzymatic antioxidants (e.g., glutathione) significantly decreased in cells. However, W-TS pretreatment, at the maximum tested concentration, significantly decreased intracellular ROS and malondialdehyde (MDA) levels, and increased superoxide dismutase and glutathione levels in the cells. At this same concentration, W-TS did not show cytotoxicity. Type 1 procollagen and MMP-1 released were quantified using RT-PCR techniques. The results showed that W-TS protected type 1 procollagen against UVB-induced depletion in fibroblast cells in a dose-dependent manner via inhibition of UVB-induced MMP-1. Taken together, the results of the study suggest that W-TS effectively inhibits UVB-induced photoaging in skin fibroblasts by its strong anti-oxidant ability.

Effects of Shinsuwisaengtang on Antioxidant Activity and Inhibition of Phototoxicity by UVB Irradiation (신수위생탕(神授衛生湯)이 UVB 조사에 의한 광독성억제활성에 대한 효과연구)

  • Kim, Ee-Hwa;Kim, Yong-Min;Kim, Hee-Taek
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.31 no.1
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    • pp.1-11
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    • 2018
  • Objectives : The purpose of this study is to investigate the effect of Shinsuwisaengtang (SSWST) extracts on antioxidant activity and inhibition of phototoxicity as a medicine for skin damage due to ultra violet stimulation. Methods : To determine the cytotoxicity of Hs68 cells from SSWST extracts, we investigated cell viability by MTT assay. To determine the protective effect of phototoxicity, we investigated cell viability after UVB radiation. The DPPH radical scavenging activity was examined to determine the antioxidant effect of SSWST extracts. Hoechst 33258 staining was performed to observe the protective effect of SSWST on UVB. Results : The cytotoxicity of SSWST extracts in Hs68 cells was not appeared significantly in all concentration. SSWST extracts significantly increased the viability of UVB-stimulated Hs68 cells at a concentration of 25, 50 and $100{\mu}g/ml$. SSWST extract showed higher DPPH radical scavenging than the control group. It was observed that SSWST extracts inhibited the apoptosis of the UVB-stimulated Hs68 cells through a fluorescence microscope. Conclusions : It was observed that SSWST did not induce cytotoxicity at a constant concentration and had a protective effect on phototoxicity and an antioxidant effect. Thus, it is considered that it maybe used as a medicine to cure skin damage caused by UVB and photoaging changes in the future.

Effects of Catechin-rich Green Tea Extract on the MMP-1 Activity of HaCaT Keratinocyte Cells and on UVB-induced Skin Damage in Hairless Mice (각질형성세포에서 MMP-1 활성 및 자외선 유도 무모쥐 피부손상에 대한 카테킨 고함유 녹차추출물의 영향)

  • Yang, Won Kyung;Park, Yang Chun;Kim, Bok Kyu;Choi, Jeong June;Ryu, Geon Seek;Kim, Seung Hyung
    • Korean Journal of Medicinal Crop Science
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    • v.27 no.2
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    • pp.143-150
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    • 2019
  • Background: Skin is an organ that protects the human body from various environmental stimuli that can induce immune system activation. Skin aging can be largely divided into two categories: physiological aging, which is caused by the a decreased physiological function of the skin and structural changes with aging, and photoaging, which is caused by the chemical stress induced by external stimuli such as ultraviolet (UV) radiation. Methods and Results: The objective of this study was to investigate the anti-wrinkle and UV protective effect of catechin-rich green tea extract (CGTE) in activated keratinocyte (HaCaT cells) and UV-induced skin damage in hairless mice. The results showed that CGTE inhibits the tumor necrosis factor-alpha interferon-gamma ($TNF-{\alpha}+IFN-{\gamma}$)-induced expression of matrix metalloproteinase (MMP)-1 in HaCaT cells. In addition, the CGTE treatment significantly reduced wrinkle formation, epidermal thickness, collagen deposition, and transepidermal water loss in dorsal skin irradiated with UVB. However, the ${\beta}$-glucosidase activity was significantly increased. The CGTE treatment inhibits mRNA expression and enzyme activity of MMP-2 and MMP-9 in the dorsal skin irradiated with UVB. Conclusions: It is expected that CGTE can be effectively used as a functional food and cosmetic ingredient to improve skin moisture retention and reduce wrinkle formation.