Intramelanocytic Acidification Plays a Role in the Antimelanogenic and Antioxidative Properties of Vitamin C and Its Derivatives

• Published in: Oxidative medicine and cellular longevity Vol. 2019; no. 2019; pp. 1 - 14
• Main Authors: Shi, Ying, Luo, Long-Fei, Jiang, Shan, Su, Meng-Yun, Miao, Fang, Lei, Tie-Chi
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2019; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Acidification; Acids; Ammonium compounds; Ammonium paratungstate; Animals; Antioxidants - metabolism; Ascorbic Acid - analogs & derivatives; Ascorbic Acid - metabolism; Biosynthesis; Cell culture; Cell Differentiation; Cell Line; Cosmetics; Cytoplasm - chemistry; Cytoplasm - metabolism; Dermatology; Digital cameras; Enzymes; Free radicals (Chemistry); Humans; Hydrogen-Ion Concentration; Melanins - metabolism; Melanocytes - physiology; Melanoma; Melanosomes - metabolism; Mice; Mice, Inbred C57BL; Monophenol Monooxygenase - metabolism; Oxidative stress; Phosphates; Proteins; Skin; Skin cancer; Skin Lightening Preparations - metabolism; Skin Pigmentation; Sodium-Coupled Vitamin C Transporters - genetics; Sodium-Coupled Vitamin C Transporters - metabolism; Up-Regulation; Venture capital; Vitamin C; China; United States > US
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2019/2084805

Although vitamin C (VC, L-ascorbic acid) has been widely used as a skin lightening agent for a long time, the mechanism by which it inhibits melanogenesis remains poorly understood. It is well-documented that the intramelanocytic pH is an important factor in regulating tyrosinase function and melanosome maturation. The activity of tyrosinase, the rate-limiting enzyme required for melanin synthesis, is generally minimal in an acidic environment. Given that VC is an acidic compound, we might speculate that the intracellular acidification of melanocytes induced by VC likely reduces melanin content through the suppression of tyrosinase activity. The results of this study reveal that treatment of melanocytes with VC or its derivatives, magnesium ascorbyl phosphate (MAP) and 3-O-ethyl-L-ascorbic acid (AAE), resulted in significant decreases in the tyrosinase activity and melanin content and in the levels of intracellular reactive oxygen species (ROS), indicating that VC and its derivatives possess antimelanogenic and antioxidative activities. Western blotting analysis indicated that VC, MAP, and AAE exert their antimelanogenic activity by inhibiting the tyrosinase activity rather than by downregulating the expression of melanogenic proteins such as tyrosinase, premelanosome protein 17 (Pmel17) and microphthalmia-associated transcription factor (MITF). Further, we found that the reduced tyrosinase activity of melanocytes treated with VC or its derivatives could be reactivated following intracellular neutralization induced by ammonium chloride (NH4Cl) or concanamycin A (Con A). Finally, we examined the expression of sodium-dependent VC transporter-2 (SVCT-2) using western blotting and qPCR, which revealed that there was a significant increase in the expression of SVCT-2 in melanocytes following treatment with VC. VC-mediated intracellular acidification was neutralized by phloretin (a putative SVCT-2 inhibitor) in a dose-dependent manner. Taken together, these data show that VC and its derivatives suppress tyrosinase activity through cytoplasmic acidification that potentially results from enhanced VC transmembrane transport via the VC transporter SVCT-2.