Heat shock, also

Exposure of neutrophils to heat shock also results in the synthesis of HSPs and a decrease in their ability to generate reactive oxidants. This is not due to cell death, because the response is reversible and other cellular functions are unaffected. For example, after 20 min exposure at 45 °C, the NADPH oxidase is non-functional, but arachidonic acid release is 73% of control values and PGE2 formation is unaffected. Oxidase activity returns to normal levels 150 min later. Several HSPs are synthesised (e.g. hsp70 and hsp85 at 41 °C, hsp48 and hsp60-65 at 43 °C). (The hsp numbers refer to the relative molecular masses of the proteins.)... 

In this section we shall look for evidence that imperfections in the synchrony, first of division then of DNA replication, reflect the fact that, in this system, cells can engage in DNA replication beyond a critical time limit antecedent to the time when most cells show synchronous division. In a preceding section it was reported that asynchronous entry of the cells into DNA replication continued for 40 or so minutes after the end of heat shocks. Also, evidence was presented that there is a time point 35 or so minutes before the shocks are ended, after which no cell that takes part in synchronous division at its peak can have entered into DNA synthesis. What is then the contribution to synchronous division of the fraction of cells that in fact enter DNA synthesis in the critical 1.25-hour interval between the two indicated times These cells will not have had time to finish S and normal G2 before they are supposed to participate in the first synchronous division. We shall see that in fact they contribute negatively to the synchrony, either by dividing later than at the time when synchronous division is at its peak or by not dividing at all. 

Phosphorylation of HSF substantially enhances the transcriptional activity of HS gene expression which may be up to 100-fold of basal levels after HSFl binds to the promoter element. Heat shock will increase the C-terminal-domain-kinase activity in cell extracts, and this action may enhance the activity of RNA polymerase II that is bound to HS genes (Legagneux et al., 1990). Whether this kinase activity also affects HSFl phosphorylation is not known, but increased HS gene expression appears to occur as long as HSFl is bound to the promoter region. The CTD kinase complex contains multiple proteins, and it is quite possible that one or more of these proteins is also regulated by stress. 

HS also affects ribonucleoproteins. Overall, there is a decrease in the pro-tein/RNA ratio. Antibodies against certain ribonucleoproteins have been used as a probe in heat shocked cells and these demonstrate a loss of some RNA particles normally seen at 37 °C. 

Most medical students look askance at thermobiology. We think this is a mistake hence, we have included a section dealing with this subject. This brings us to the chapter on the heat shock response which at the very outset makes clear that many stressors besides heat are known to result in heat shock gene expression. Many of the heat shock proteins occur in unstressed cells and some of them behave as chaperones. These proteins also reach high levels in a wide range of diseases... 

Figure 36-4. Illustration of the tight correlation between the presence of RNA polymerase II and RNA synthesis. A number of genes are activated when Chirono-mus tentans larvae are subjected to heat shock (39 °C for 30 minutes). A Distribution of RNA polymerase II (also called type B) in isolated chromosome IV from the salivary gland (at arrows). The enzyme was detected by immunofluorescence using an antibody directed against the polymerase. The 5C and BR3 are specific bands of chromosome IV, and the arrows indicate puffs. B Autoradiogram of a chromosome IV that was incubated in H-uridine to label the RNA. Note the correspondence of the immunofluorescence and presence of the radioactive RNA (black dots). Bar = 7 pm. (Reproduced, with permission, from Sass H RNA polymerase B in polytene chromosomes. Cell 1982 28 274. Copyright 1982 by the Massachusetts Institute of Technology.)...

Hormone response elements (for steroids, T3, retinoic acid, peptides, etc) act as—or in conjunction with— enhancers or silencers (Chapter 43). Other processes that enhance or silence gene expression—such as the response to heat shock, heavy metals (Cd and Zn +), and some toxic chemicals (eg, dioxin)—are mediated through specific regulatory elements. Tissue-specific expression of genes (eg, the albumin gene in liver, the hemoglobin gene in reticulocytes) is also mediated by specific DNA sequences. 

It has been postulated that Chlamydia may produce a heat shock protein that causes tissue damage through a delayed hypersensitivity reaction. C. trachomatis may also possess DNA evidence of toxin-like genes that code for high-molecular-weight proteins with structures similar to Clostridium difficile cytotoxins, enabling inhibition of immune activation. This may explain the observation of a chronic C. trachomatis infection in subclinical PID. 

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