HUANG, Z; TUNNACLIFFE, A; Univ. of Cambridge, UK; Univ. of Cambridge, UK: Molecular Response of Human Cells to Dehydration

Although there is an increasing interest in anhydrobiotic engineering using mammalian cells, little information is available on how they sense and respond to desiccation, or indeed whether they are able to do so. We have recently investigated the effect of air drying on stress signalling pathways and gene induction in human embryonic kidney cells (T-REx 293), in comparison with another type of dehydration stress, hyperosmolarity. A well-conserved signalling network involves mitogen-activated protein kinases (MAPKs), which modulate cellular response to a variety of stresses. Activation of MAPKs by desiccation was shown by Western blotting to be rapid, within 30 min of exposing cells to 98% relative humidity (RH), and thus occurs equally as fast as the response to hyperosmotic shock. Gene induction by desiccation has also been revealed by microarray and quantitative real-time PCR analyses. Most of the highly induced genes were those encoding zinc finger transcriptional regulators and/or those involved in cell death and survival pathways, e.g. EGR1, EGR3, IER3, SNAI1, RASD1, and GADD45B. Some of these genes were induced up to 100-400 fold within 6-16 h of desiccation when 30-90% cells survived the drying regime (98% RH, 37�C). Interestingly, however, the hyperosmotically responsive genes AR, BGT1 and SMIT, which encode proteins governing organic osmolyte accumulation to mitigate hyperosmotic water loss, were not significantly induced by desiccation. These data demonstrate that human cells can respond rapidly to desiccation by MAPK activation and gene induction, probably involving different cell death and survival pathways, but the response only partially overlaps with that to hyperosmotic stress.