P33 Quantification of metabolic pathways in human hair follicles and their response to caffeine and N,N-dimethylglycine

Abstract Introduction and aims Androgenetic alopecia (AGA) is a genetically determined hereditary precondition to hair loss. Hair follicles (HFs) engage in aerobic glycolysis, with preferential metabolism to glucose despite oxygen presence. Dermal papilla cells (DPCs) from AGA are sensitive to oxidative stress and mitochondria-related genes are upregulated in balding cell lines suggesting a potential switch to more oxidative metabolism and free radical generation. Caffeine a potent phosphodiesterase inhibitor resulting in increased cyclic AMP has been used as treatment for AGA via increased glucose metabolism by glycolysis. N,N-dimethylglycine (DMG) is a derivative of glycine known for anti-inflammatory and antioxidant properties; shown to promote vasodilation by inducing the release of nitric oxide from endothelial cells. To investigate the effects of caffeine and DMG on the metabolism of immortalized balding (IB) and nonbalding (IN) DPC. Methods Dose–response experiments investigated the effects of caffeine and DMG on toxicity; lactate dehydrogenase (LDH) and cell viability (MTT). A Ca²+ influx assay was used to establish that IB and IN were responsive to treatments. Results IB and IN DPC showed no significant LDH cytotoxic effects from either treatment compared with controls. The percentage of viable DPC treated with the optimal dose of caffeine (5 µmol L−1) and DMG (30 µmol L−1) were the same as untreated cells (N = 3). Caffeine (5 µmol L−1) and DMG (30 µmol L−1) stimulated a significant increase in Ca²+ influx indicating that both DPCs were responsive to treatment. ATP was used as an experimental control to induce Ca²+ influx, with clear activation, indicating intracellular-Ca²+ flux was via ATP regulated Ca²+channels in DPCs. Conclusions Treatments of caffeine and DMG did not cause toxicity or alter viability of IB and IN DPC and could stimulate Ca²+ influx. Metabolomic studies will now be undertaken to investigate differences in IB and IN phenotypes and the effects of caffeine and DMG on DPC metabolism.