Effect of Cl- on tyrosinase: complex inhibition kinetics and biochemical implication.
Tyrosinase plays a core role in melanogenesis of the various organisms. Therefore, the regulation of the tyrosinase activity is directly related with melanin synthesis. In this study, we investigated the Cl(-)-induced inhibition of human tyrosinase and the potent role of Cl(-) as a negative regulator in melanogenesis. For the inhibition kinetic studies, human tyrosinase was differently prepared from the TXM13 melanotic cells as well as from cells that had undergone gene transfection. We found that Cl(-) inhibited tyrosinase in a slope-parabolic competitive manner and tyrosinase gene transfection into HEK293 cell significantly down-regulated the expression levels of solute carrier family 12, member 4 (potassium/chloride transporters, SLC12A7) and solute carrier family 12, member 7 (potassium/chloride transporters, SLC12A7), which are known to be Cl(-) transporters. From the results of the inhibition kinetic studies and the Cl(-) transporter expression level, we suggested that Cl(-) might act as a potent regulatory factor in melanogenesis. It is worth notice that a high content of Cl(-) exists physiologically and tyrosinase reacts sensitively to Cl- in a complex interaction manner.
Han
Hon-Yan
HY
Department of Biology, College of Life Sciences, Soochow University, Suzhou 215123, PR China.
Lee
Jae-Rin
JR
Xu
Wei-An
WA
Hahn
Myong-Joon
MJ
Yang
Jun-Mo
JM
Park
Yong-Doo
YD
D000818:Animals; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism*; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D000096922:K Cl- Cotransporters
D002712:Chlorides; D008543:Melanins; D014442:Monophenol Monooxygenase; D027981:Symporters; D000096922:K Cl- Cotransporters; C119651:SLC12A7 protein, human