Inhibition of melanogenesis by jineol from Scolopendra subspinipes mutilans via MAP-Kinase mediated MITF downregulation and the proteasomal degradation of tyrosinase

被引:52
作者
Alam, Md Badrul [1 ]
Bajpai, Vivek K. [2 ]
Lee, JungIn [3 ]
Zhao, Peijun [1 ]
Byeon, Jung-Hee [1 ]
Ra, Jeong-Sic [1 ]
Majumder, Rajib [4 ,5 ]
Lee, Jong Sung [6 ]
Yoon, Jung-In [6 ]
Rather, Irfan A. [2 ]
Park, Yong-Ha [2 ]
Kim, Kangmin [7 ]
Na, MinKyun [3 ]
Lee, Sang-Han [1 ]
机构
[1] Kyungpook Natl Univ, Dept Food Sci & Biotechnol, Grad Sch, Daegu 41566, South Korea
[2] Yeungnam Univ, Dept Appl Microbiol & Biotechnol, Microbiome Lab, Gyongsan 38541, Gyeongbuk, South Korea
[3] Chungnam Natl Univ, Coll Pharm, Daejeon 34134, South Korea
[4] Macquarie Univ, Dept Biol Sci, Sydney, NSW 2109, Australia
[5] EMAI, Biosecur & Food Safety, NSW Dept Primary Ind, Menangle, NSW 2567, Australia
[6] Kcellbio, Seoulsoop Kolon Digital Tower,Seongsuil Ro 4 Gil, Seoul 04713, South Korea
[7] Chonbuk Natl Univ, Div Biotechnol, Coll Environm & Bioresource Sci, 79 Gobong Ro, Iksan Si 570752, Jeonbuk, South Korea
关键词
POSSIBLE INVOLVEMENT; MELANIN SYNTHESIS; NITRIC-OXIDE; ACID; PIGMENTATION; MODULATION; PATHWAYS; PI3K/AKT; MEK/ERK; HORMONE;
D O I
10.1038/srep45858
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In this study, the authors investigated the anti-melanogenic effects of 3,8-dihydroxyquinoline (jineol) isolated from Scolopendra subspinipes mutilans, the mechanisms responsible for its inhibition of melanogenesis in melan-a cells, and its antioxidant efficacy. Mushroom tyrosinase activities and melanin contents were determined in melan-a cells, and the protein and mRNA levels of MITF, tyrosinase, TYRP-1, and TYRP-2 were assessed. Jineol exhibited significant, concentration-dependent antioxidant effects as determined by DPPH, ABTS, CUPRAC, and FRAP assays. Jineol significantly inhibited mushroom tyrosinase activity by functioning as an uncompetitive inhibitor, and markedly inhibited melanin production and intracellular tyrosinase activity in melan-a cells. In addition, jineol abolished the expressions of tyrosinase, TYRP-1, TYRP-2, and MITF, thereby blocking melanin production and interfering with the phosphorylations of ERK1/2 and p38. Furthermore, specific inhibitors of ERK1/2 and p38 prevented melanogenesis inhibition by jineol, and the proteasome inhibitor (MG-132) prevented jineol-induced reductions in cellular tyrosinase levels. Taken together, jineol was found to stimulate MAP-kinase (ERK1/2 and p38) phosphorylation and the proteolytic degradation pathway, which led to the degradations of MITF and tyrosinase, and to suppress the productions of melanin.
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页数:12
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