Gene Expression Profiling of Human Heat Stress: Effects of Aging and Gender

Project Summary:

The adaptive response to heat stress, as discussed above, is clearly an extremely complex phenomenon that until recently has been viewed from the narrow perspective of only one or at most, a few genes operating at one time. The completion of the human genome and the emergence of new technologies, such as DNA microarrays, allow tens of thousands of specific DNA or RNA sequences to be detected simultaneously in any tissue sample in a single experiment40-42 . A cDNA array that contains only 207 stress related genes in heat stressed rats showed that the molecular basis of heat stress goes beyond the acute phase and heat shock responses, and include up- regulation of genes that encode for oxidants and antioxidants, cell growth and death signaling 38.  More importantly,  this study is a proof of concept that  micro arrays can help pinpoint the molecular changes (blunted heat shock response and increased oxidative stress ) that occur during aging and which result in increased susceptibility to heat38.  Likewise, in human (4 soldiers) suffering from exertional heat injury, a DNA microarrays that comprises 12,600 sequences, identified more than 300 transcripts that are two-fold or down-regulated confirming the complexity of the adaptative response to heat stress43. Therefore, in the present investigation, we took a broadscale genomic (full genome scanning) approach combined with proteomic.  We hypothesize that the application of two combined profiling approaches (proteomics and genomics) to this study will give a broader insight into the molecular basis of heat stress by characterizing the gene and protein expression patterns of adaptive response of heat stressed normal volunteers. Such study will help to identify the molecular basis that underline the loss of tolerance to heat of elderly versus young and female versus male subjects . This knowledge could form the basis of improved prevention of heatstroke. This is particularly important as from historical data, the Hajj will enter in the hot cycle as early as next pilgrimage for the next15 years8, 9.