25-hydroxycholesterol acts in the Golgi compartment to induce degradation of tyrosinase

Pigment Cell Research
Andrea M HallSeth J Orlow

Abstract

Oxysterols play a significant role in cholesterol homeostasis. 25-Hydroxycholesterol (25HC) in particular has been demonstrated to regulate cholesterol homeostasis via oxysterol-binding protein and oxysterol-related proteins, the sterol regulatory element binding protein, and the rate-limiting enzyme of cholesterol biosynthesis, hydroxymethylglutaryl coenzyme A reductase. We have examined the effect of 25HC on pigmentation of cultured murine melanocytes and demonstrated a decrease in pigmentation with an IC(50) of 0.34 microM and a significant diminution in levels of melanogenic protein tyrosinase. Pulse-chase studies of 25HC-treated cells demonstrated enhanced degradation of tyrosinase, the rate-limiting enzyme of melanin synthesis, following endoplasmic reticulum (ER) and Golgi maturation. Protein levels of GS28, a member of an ER/cis-Golgi SNARE protein complex, were also diminished in 25HC-treated melanocytes, however levels of the ER chaperone calnexin and the cis-Golgi matrix protein GM130 were unaffected. Effects of 25HC on tyrosinase were completely reversed by 4 alpha-allylcholestan-3 alpha-ol, a sterol identified by its ability to reverse effects of 25HC on cholesterol homeostasis. Finally, the addition of 25HC to lip...Continue Reading

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Citations

Aug 25, 2006·Journal of Biomolecular Structure & Dynamics·Yong-Doo ParkJun-Mo Yang
Jan 9, 2010·International Journal of Molecular Sciences·Hideya AndoVincent J Hearing
Jun 15, 2011·Experimental Cell Research·Wenbin ZhongDaoguang Yan
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Jan 20, 2006·Pigment Cell Research·Ning Wang, Daniel N Hebert
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Oct 27, 2016·International Journal of Cosmetic Science·S-J LeeI-G Kim
Nov 2, 2020·Survey of Ophthalmology·Siyin LiuMervyn G Thomas

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