The Osmolyte Strategy of Normal Human Keratinocytes in Maintaining Cell Homeostasis

Abstract

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.

The Change of Taurine Transport in Osteocytes by Oxidative Stress, Hypertonicity and Calcium Channel Blockers

“…For the patients with diabetes mellitus, they are likely to be in high osmotic pressure condition since the level of glucose in the blood is high. In the condition of high osmotic pressure, it is reported that mRNA expression of TauT, betaine transporter (BGT-1) and sodium/myo-inositol co-transporter (SMIT) is changed and uptake of taurine, betaine and myo-inositol is elevated in many tissues (Warskulat et al, 1997;Takeuchi et al, 2000;Shioda et al, 2002;El-Sherbeny et al, 2004;Warskulat et al, 2004). Moreover, there are some papers that the mRNA expression of TauT and BGT-1 and the uptake of taurine and betaine into the kidney elevated under high osmotic pressure (Uchida et al, 1992;Yamauchi et al, 1992).…”

The Osmolyte Taurine Protects against Ultraviolet B Radiation-Induced Immunosuppression

“…Despite its high abundance in tissues, and its manifold functions in cellular homeostasis, little is known until now about the role(s) of the osmolyte taurine in skin cells (15,35). Prompted by our finding that uptake of taurine and expression of the transporter for taurine, TAUT, are up-regulated by UVB exposure in keratinocytes (15), we studied whether taurine deficiency in the skin of mice influences their susceptibility to UVB-induced immunosuppression.…”

“…In this regard we have recently shown that epidermal keratinocytes possess an osmolyte strategy, i.e., upon exposure to hyperosmotic stress keratinocytes accumulate the osmolyte taurine (15). In these studies, taurine uptake was associated with an increased expression of the specific transporter for taurine, i.e., TAUT.…”

Topical Phenytoin in Neuralgic Pain, Peripheral Modulation of Central Sensitization: Two Case Reports

“…GABA most probably also plays a role in the physiology of keratinocytes, and is observed within the keratinocyte [40][41][42]. One of the enzymes involved in the synthesis of GABA has been identified in the skin [43].…”