In response to heat shock or other metabolic insults, an increased expression of different heat shock proteins (hsps) and, in particular, members of the hsp7O family is observed in human cells. Using two-dimensional electrophoresis, we compared the pattern of hsp7O synthesis in human fibroblast cell lines isolated from two contrasting groups of individuals. The first group was represented by native Turkmen living in the hot desert of Middle Asia; the second group consisted of Russians living in moderate climatic regions of European Russia. This analysis has shown that fibroblasts isolated from Turkmen after severe heat shock exhibited intensive synthesis of all hsps in parallel with synthesis of many other cellular proteins, while only trace synthesis of hsps was observed in the second group (Russians). Surprisingly, Northern analysis of RNA synthesis failed to reveal any differences between the two groups after heat shock treatment. When survival of fibroblasts after severe heat shock treatment was assessed by colony formation assay, the cells of the first group exhibited significantly higher survival rates.All organisms studied to date respond to an elevation of 5°C or more above their normal physiological temperature with the rapid synthesis of a highly conserved group of proteins [heat shock proteins (hsps)]. It is a widely held assumption that the purpose of the heat shock response is to protect organisms from the toxic effects of heat and other forms of stress (1, 2). hsps and, in particular, members of the hsp70 family have been implicated as essential components of protein maturation and transport (3, 4). These proteins have been shown to participate as molecular chaperones, facilitating the early events of protein synthesis, protein folding, and perhaps higher-ordered protein assembly (5,6
MATERIALS AND METHODSTissue Culture Cells of Different Origin. Diploid skin fibroblasts of two different human groups were used in the investigation. The first group was represented by Turkmen aborigines, a tribe with a certain level of inbreeding inhabiting for many generations (about 2500 years) the extremely hot and dry deserts of Middle Asia. The second group consists of Russians living in moderate climatic regions of European parts of the former U.S.S.R. Fibroblast cultures from 7-10 volunteers were compared in both groups.Heat Shock and Protein Purification. Fibroblasts used in all experiments were maintained at 37°C for 10-15 passages. The cells were cultured in Eagle's medium supplemented with 5% fetal calf serum and 5% fetal bovine serum. Each individual culture was subdivided into four flasks and heat shocked at 42.5°C in a circulating water bath for 2, 4, and 6 h. The fourth flask (control) was kept at 37°C in parallel with cells undergoing heat shock treatment, and the control cells were harvested at the end of the heat shock experiment. After heat shock, the cells were rinsed with balanced Hanks' salt medium and labeled for 1 h at 37°C in the same salt solution containing 14C-labeled amino acids ...
The intensity of heat shock protein synthesis by splenocytes is assessed in mice of two strains with genetically different sensitivity to antiproliferative effect of alkylating effect of maphosphamide. The content and de novo production of heat shock proteins in resistant BALB/c mice are higher than in sensitive DBA/2 mice. Exposure to heat shock increases cell resistance to antiproliferative action of maphosphamide.
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