The osmolyte strategy of normal human keratinocytes in maintaining cell homeostasis.

Compatible organic osmolytes, such as betaine, myoinositol, and taurine, are involved in cell volume homeostasis as well as in cell protection, for example, against oxidative stress. This so-called osmolyte strategy requires the expression of specific osmolyte transporting systems such as the betaine/gamma-amino-n-butyric acid (GABA) transporter, the sodium-dependent myoinositol transporter and the taurine transporter (TAUT). In contrast to liver, kidney, and neural cells, nothing is known about osmolytes in the skin. Here we report that primary normal human keratinocytes (NHK) express mRNA specific for the betaine/GABA transporter, for the sodium-dependent myoinositol transporter and for the TAUT. In comparison to normoosmotic (305 mosmol per L) controls, a 3-5-fold induction of mRNA expression for the betaine/GABA-, the sodium-dependent myoinositol- and the TAUT was observed within 6-24 h after hyperosmotic exposure (405 mosmol per L). Expression of osmolyte transporters was associated with an increased uptake of radiolabeled osmolytes. Conversely, hypoosmotic (205 mosmol per L) stimulation induced significant efflux of these osmolytes. Exposure to ultraviolet B (290-315 nm) or ultraviolet A (340-400 nm) radiation, which are major sources of oxidative stress in skin, significantly stimulated osmolyte uptake. Increased osmolyte uptake was associated with upregulation of mRNA steady-state levels for osmolyte transporters in irradiated cells. These studies demonstrate that NHK possess an osmolyte strategy, which is important for their capacity to maintain cell volume homeostasis and seems to be part of their response to UV radiation.