4.6 Article

GIF-2209, an Oxindole Derivative, Accelerates Melanogenesis and Melanosome Secretion via the Modification of Lysosomes in B16F10 Mouse Melanoma Cells

期刊

MOLECULES
卷 27, 期 1, 页码 -

出版社

MDPI
DOI: 10.3390/molecules27010177

关键词

oxindole; SU5205; melanogenesis; melanosome; tyrosinase; TYRP-1; lysosome

资金

  1. Japan Society for the Promotion of Science (JSPS) [20K05703, JPJSBP120218102]
  2. Japan Science and Technology Agency (JST) [JPMJTM20E8]
  3. Nakatani Foundation (R3)
  4. Japan Dairy Association (J-Milk) (R3)
  5. Grants-in-Aid for Scientific Research [20K05703] Funding Source: KAKEN

向作者/读者索取更多资源

The oxindole derivative GIF-2209 promotes melanogenesis and melanosome secretion by regulating multiple mechanisms, such as upregulating TYR expression, suppressing TYRP-1 protein levels, inducing lysosome expansion and redistribution, and accelerating autophagy.
Melanogenesis and melanosome secretion are regulated by several mechanisms. In this study, we found that the oxindole derivative GIF-2209 accelerated melanogenesis associated with the discrimination in the expression and intracellular distributions of two melanogenic enzymes, tyrosinase (TYR) and tyrosinase-related protein-1 (TYRP-1). GIF-2209 upregulated the expression of TYR via a microphthalmia transcription factor (MITF)-independent mechanism, leading to high expression of protein. In contrast, GIF-2209 did not alter the mRNA levels of TYRP-1 and suppressed its protein levels. GIF-2209 induced the dissociation of TYR from TYRP-1 but did not alter the association between TYR and CD63, a melanosome and lysosome marker. The protein levels of CD63 were also upregulated by GIF-2209. GIF-2209 induced lysosome expansion and redistribution in all areas of the cytosol, accompanied by autophagy acceleration (upregulation of LC3BII protein levels and downregulation of p62 protein levels). In addition, GIF-2209 stimulated the secretion of melanosomes containing high levels of TYR, TYRP-1, and CD63 proteins. The GIF-2209 mediated melanosome secretion was sensitive to the lysosome inhibitor chloroquine. These results suggest that GIF-2209 may activate lysosomal functions with TYR gene expression, while it accelerates melanosome secretion, which finally leads to the depletion of intracellular melanogenic enzyme, especially TYRP-1 protein.

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