Biol. Pharm. Bull. 29(1) 14—16 (2006)

inhibited by antioxidants, like a-tocopherol and hydrocoumarins, and that reduced glutathione (GSH), an important biological reductant, plays a role in the modulation of the melanogenic process. Melanogenesis, which is catalyzed enzymatically by the key enzyme, tyrosinase, is also influenced by other non-enzymatic factors such as ultraviolet rays and a-melanocytestimulating hormone (a-MSH). In the case of a-MSH-induced melanogenesis, the enhancement of tyrosinase activity, tyrosinase mRNA, and intracellular cyclic AMP (cAMP) were observed. The requirement of cAMP for melanogenesis is quite clear for pigmentation. cAMP also increases tyrosinase mRNA and promotes increased microphthalmia transcription factor (MITF) expression. MITF is a melanocyte-specific transcription factor crucial for melanocyte survival, development and differentiation through the activation of protein kinase A (PKA). PKA is a serine/threonine kinase that is an inactive tetramer consisting of two regulatory subunits and two catalytic subunits, and its activation occurs by the binding of cAMP to its regulatory subunits and then releasing its catalytic subunits from the regulatory subunits. Recently, we reported that 4,4 -dihydroxybiphenyl (44 BP) has a melanogenesis inhibitory effect through the inhibition of tyrosinase and reduction of melanin content. However, the underlying process by which tyrosinase activity and melanogenesis were inhibited by 44 -BP was not elucidated. In this current study, we attempted to investigate the effect of 44 -BP on major cellular regulators involved in melanogenesis in B16 melanoma cells (B16 cells). The analysis was carried out by quantifying amounts of tyrosinase and MITF proteins, cAMP levels, phosphorylated PKA, and GSH and oxidized glutathione (GSSG) levels.