1 September 2004 Molecular Mechanism(s) for UV-B Irradiation–Induced Glutathione Depletion in Cultured Human Keratinocytes
Ming Zhu, G. Tim Bowden
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Glutathione (GSH) plays a central role in maintenance of cellular redox homeostasis and protection against oxidative injury. Ultraviolet B (UV-B) irradiation–induced GSH depletion is believed to be involved in the pathogenesis of several cutaneous disorders. In this study, the molecular mechanism(s) of UV-B–induced GSH depletion was investigated in cultured human keratinocytes, HaCaT cells. We found that UV-B irradiation caused GSH depletion in a dose- and time-dependent manner in HaCaT cells. The mechanistic studies showed that UV-B–induced GSH depletion did not result from the GSH efflux. UV-B irradiation appeared to cause a slight decrease in enzymatic activity of γ-glutamate cysteine ligase (GCL), a rate-limiting enzyme in GSH biosynthesis. UV-B irradiation resulted in the GCL cleavage through the activation of a caspase cascade. Inhibition of total caspase activity by the general caspase inhibitor, zVAD-fmk, partially reversed the UV-B–induced GSH depletion. More importantly, we found that UV-B irradiation could dramatically decrease the cystine uptake through the functional inhibition of the system Xc, a cystine transporter on the cell membrane. The results suggest that the inactivation of cystine transporter system Xc was a major contributor to the UV-B–mediated decrease of GSH levels in human keratinocytes.

Ming Zhu and G. Tim Bowden "Molecular Mechanism(s) for UV-B Irradiation–Induced Glutathione Depletion in Cultured Human Keratinocytes," Photochemistry and Photobiology 80(2), 191-196, (1 September 2004). https://doi.org/10.1562/2004-02-26-RA-091.1
Received: 26 February 2004; Accepted: 1 June 2004; Published: 1 September 2004

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