Abstract：
:Melanin in the epidermis is known to ultimately regulate human skin pigmentation. Recently, we exploited a phenotypic-based screening system composed of ex vivo human skin cultures to search for effective materials to regulate skin pigmentation. Since a previous study reported the potent inhibitory effect of metformin on melanogenesis, we evaluated several biguanide compounds. The unexpected effect of phenformin, once used as an oral anti-diabetic drug, on cutaneous darkening motivated us to investigate its underlying mechanism utilizing a chemical genetics approach, and especially to identify alternatives to phenformin because of its risk of severe lactic acidosis. Chemical pull-down assays with phenformin-immobilized beads were performed on lysates of human epidermal keratinocytes, and subsequent mass spectrometry identified 7-dehydrocholesterol reductase (DHCR7). Consistent with this, AY9944, an inhibitor of DHCR7, was found to decrease autophagic melanosome degradation in keratinocytes and to intensely darken skin in ex vivo cultures, suggesting the involvement of cholesterol biosynthesis in the metabolism of melanosomes. Thus, our results validated the combined utilization of the phenotypic screening system and chemical genetics as a new approach to develop promising materials for brightening/lightening and/or tanning technologies.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Takano K,Hachiya A,Murase D,Kawasaki A,Uda H,Kasamatsu S,Sugai Y,Takahashi Y,Hase T,Ohuchi A,Suzuki Tdoi
10.3390/ijms21041451subject
Has Abstractpub_date
2020-02-20 00:00:00issue
4issn
1422-0067pii
ijms21041451journal_volume
21pub_type
杂志文章abstract：:Wound healing is a multistep process with four overlapping but distinct stages: hemostasis, inflammation, proliferation, and remodeling. An alteration at any stage may lead to the development of chronic non-healing wounds or excessive scar formation. Impaired wound healing presents a significant health and economic bu...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2018-10-18 00:00:00
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journal_title：International journal of molecular sciences
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doi：10.3390/ijms15010798
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abstract：:Gastric cancer (GC) is the fifth most common cancer worldwide and the second leading cause of cancer-related death. GC is usually diagnosed at an advanced stage due to late presentation of symptoms. Therefore, there is a need for establishing more sensitive and specific markers useful in early detection of the disease...
journal_title：International journal of molecular sciences
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doi：10.3390/ijms21228456
更新日期：2020-11-10 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2018-12-17 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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更新日期：2017-02-09 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2013-11-18 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms17020198
更新日期：2016-02-02 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2020-07-11 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2019-12-21 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2019-04-14 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2019-03-14 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20061261
更新日期：2019-03-13 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2012-10-18 00:00:00
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journal_title：International journal of molecular sciences
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doi：10.3390/ijms20246335
更新日期：2019-12-16 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2020-08-23 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2014-09-23 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2019-09-25 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2017-11-29 00:00:00
abstract：:Substantial efforts are underway for prevention of early stages or recurrence of colorectal cancers (CRC) or new polyp formation by chemoprevention strategies. Several epidemiological, clinical and preclinical studies to date have supported the chemopreventive potentials of several targeted drug classes including non-...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms19082332
更新日期：2018-08-08 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20061289
更新日期：2019-03-14 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2020-04-07 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2020-03-06 00:00:00
abstract：:The recognition of cell surface glycans by lectins may be critical for the innate and adaptive immune responses. ArtinM, a d-mannose-binding lectin from Artocarpus heterophyllus, activates antigen-presenting cells by recognizing TLR2 N-glycans and induces Th1 immunity. We recently demonstrated that ArtinM stimulated C...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18071400
更新日期：2017-06-30 00:00:00
