078 Basic Fibroblast Growth Factor Functions as a Survival Factor for Normal Melanocytes: Significance of Human White Hair

Kenji Ohguchi, Mitsuyuki Hotta, and Yoshinori Takema, Biological Science Laboratories, Kao Corporation, Tochigi, Japan

Whitening of human scalp hair is usually a manifestation of ageing process and is caused by the disappearance of hair follicle melanocytes. We previously analysed that the expressions of various molecules in single anagen hair follicles from human white and black scalp hair. Intriguingly, basic fibroblast growth factor (basic FGF) mRNA level was observed to be down-regulated in white hair follicles, as inferred by reverse transcription-polymerase chain reaction (RT-PCR). Melanocytes are known to support the proliferation by basic FGF secreted from surrounding keratinocytes. Recently, several reports have provided evidence that basic FGF may also act as a survival (anti-apoptotic) factor for melanocytes, but the exact mechanism is not well. The present study was designed to gain more insight into the mechanisms underlying the survival function of basic FGF in normal human melanocytes. In cell culture, apoptotic cell death was initiated by the addition of oxidative stress (0.1mM hydrogen peroxide) and assessed by DNA fragmentation detection (ELISA) and LDH assay. With oxidative stress treatment, apoptotic cells increased in a time-dependent manner. The oxidative stress-induced apoptosis was inhibited in a concentrationdependent manner by basic FGF. Because recent studies have demonstrated the implication of Bcl-2 family proteins (Bcl-2, Bcl-xL, Bax, and Bak) as regulatory factors of apoptosis-signaling, changes in the contents of these proteins in melanocytes were examined. Western blot analysis revealed that the contents of Bcl-2 protein in melanocytes, a suppressive effector of apoptosis, were storongly elevated in the presence of basic FGF. Furthermore, Bcl-2 antisense oligonucleotide effectively suppressed basic FGF-induced protection from apoptosis. These findings suggest that basic FGF might be essential for the maintenance of appropriate life span of melanocytes by up-regulating intracellular Bcl-2 levels. Thus, whitening of human scalp hair can be explained, at least in part, by down-regulation of basic FGF in hair follicle.