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D A Jurivich

Publications and source records attributed to D A Jurivich.

11 recordsLinked to original sources
PubMed1997

Ultraviolet light attenuates heat-inducible gene expression.

Ultraviolet light (UV) induces a stress response mediated through transcription factors such as NF-kB and AP-1, yet little is known about its effect on other transactivators of stress gene expression such as heat shock factor (HSF1). Analysis of UV-treated HeLa cells unexpectedly revealed uncoupling of the heat shock response. UV weakly induced HSF1 into its DNA bound state and markedly attenuated heat-inducible gene expression. HSF1 was further analyzed as a potential target for the uncharacteristic uncoupling of the thermal stress response by another type of stress. Heat-inducible multimerization and nuclear translocation of HSF1 were found to be intact in UV-treated cells; however, the monomeric rather than the multimeric form of HSF1 become hyperphosphorylated by UV. This effect could be partially abolished by the antioxidant N-acetyl cysteine with partial reconstitution of hs gene expression. The reported role of a MAP kinase blockade of HSF1 transactivating properties could not be confirmed by an inhibitor of the MAP kinase pathway. Fibroblasts defective in SAP kinase activity also did not exhibit resistance to UV-inducible phosphorylation of HSF1. Two-dimensional phosphopeptide mapping of HSF1 revealed a single tryptic peptide to be affected by UV, but no new pattern of phosphorylation was evident relative to tryptic phosphopeptide profile observed in control cells. These data suggest that UV uncoupling of the hs response possibly involves steps in addition to those associated with phosphorylation the monomeric form of HSF1.

Acetylcysteine↗
PubMed1997

Attenuated stress responses in young and old human lymphocytes.

Aging generally is understood to be a period defined by altered responses to physiological stress. At the molecular level, several stress responses involving specific gene expression have been revealed, and thermal stress has been tightly linked to induction of the heat shock gene family (D.A. Jurivich. In E. Bittar (ed.), Principles of Medical Biology, Vol. 4, JAI press, San Diego, 1996, pp. 411-462). Perturbations in heat shock gene transcription consistently have been noted in senescent cells from all species examined thus far. Because heat shock proteins serve several vital functions in the immune system, changes in the thermal stress response could potentially contribute to immunosenescence. Inadequate promoter priming by the transactivator or heat shock genes, heat shock factor 1 (HSF1), is thought to account for age-dependent diminution in expression of these genes, although the exact mechanism for this loss is not clearly understood. We have found that human lymphocytes exhibit an age-dependent loss in HSF1-DNA binding, although a range of binding has been observed in both young and old donor cells. This report characterizes a subset of young and old human donor lymphocytes that are non-responders to thermal stress defined by the absence of HSF1-DNA binding after a 42 degrees C heat shock. Whole cell extracts from these donor cells have the capacity to inhibit HSF1-DNA binding when mixed with pre-activated HSF1 from HeLa cells. This inhibitory activity is lost upon heat denaturation and does not appear to be protease mediated. Serial passage of lymphoblasts recapitulates loss of heat inducible HSF1-DNA observed in old donor lymphocytes, thus suggesting that loss of replicative potential and aging lead to altered stress responses. Uncoupling of the thermal response and its potential relevance to apoptosis and aging are discussed.

Adult↗
PubMed1997

Effects of mesalamine on the hsp72 stress response in rat IEC-18 intestinal epithelial cells.

BACKGROUND & AIMS: Mesalamine has many effects and is commonly used for the treatment of inflammatory bowel diseases. Because sodium salicylate, a related compound, modulates the heat shock protein (hsp72) response in nonepithelial cells, the possibility that mesalamine confers cell protection by increasing intestinal epithelial hsp72 expression was examined. METHODS: Rat intestinal IEC-18 cells were treated with 0.3-3 mmol/L mesalamine and thermally stressed (39 degrees C-42 degrees C) for 23 minutes. The effects of mesalamine on basal expression and the threshold and time course of hsp72 thermal induction were determined. RESULTS: Although mesalamine had no effects on the basal hsp72 expression or its thermal activation threshold in IEC-18 cells, it accelerated and augmented thermal induction of hsp72 within the first 2 hours of exposure. This was associated with a transient increase in heat shock factor-heat shock element binding and enhanced cellular protection against oxidant-induced injury. In contrast, both mesalamine and sodium salicylate have been shown to lower the thermal induction threshold but not to enhance the hsp72 response in HeLa cells. CONCLUSIONS: Mesalamine augments thermal induction of the intestinal epithelial hsp72 expression in a manner that differs from that in nonintestinal epithelial cells. This effect is accompanied by increased cellular protection against oxidant injury.

Animals↗
PubMed1996

Phospholipase A2 triggers the first phase of the thermal stress response and exhibits cell-type specificity.

To understand the relationship of inflammatory and cellular stress responses, phospholipase A2 (PLA2) was examined for its role in the first phase of the transcriptional response to cellular stress. Electromobility shift analysis revealed heat shock transcription factor (HSF1)-DNA binding when HeLa S3 and Jurkat cells were exposed to exogenous PLA2. Although PLA2-inducible HSF1-DNA binding was comparable to thermal stress, it did not induce maximal heat shock gene expression. PLA2-induced HSF1 was not hyperphosphorylated relative to the heat-inducible form, thus suggesting that exogenous PLA2 affects the signal for HSF1 multimerization but not its phosphorylation. Because inflammation often involves elevated temperatures, the effect of PLA2 on thermal regulation of HSF1-DNA binding activity was examined. PLA2 exposure altered the thermal threshold for HSF1 activation, and pore-gradient gel analysis indicated that either conformational changes or other modifications of HSF1 are being induced when cells are treated by PLA2, thus creating a synergistic environment for HSF1 activation into its DNA-bound state. Surprisingly, the monocyte-like cell line, U-937, was insensitive to the action of exogenous PLA2. Neither HSF1-DNA binding or lowering of the temperature threshold for HSF1 activation was observed in PLA2-treated U-937 cells. These data suggest that inflammatory mediators such as PLA2 partially affect transcriptional switches mediating thermal stress in some cell types but not others. The purpose of HSF1 activation during inflammation and its differential induction are discussed relative to these observations.

Arachidonic Acid↗
PubMed1995

Salicylate triggers heat shock factor differently than heat.

Sodium salicylate has the unusual property of partially inducing the human heat shock response (Jurivich, D. A., Sistonen, L., Kroes, R., and Morimoto, R. I. (1992) Science 255, 1243-1245). Salicylate induces the DNA binding state of the human heat shock transcription factor (HSF), but this is insufficient to elevate heat shock gene expression. Because it is not known how HSF enhances heat shock gene expression, further analysis of the transcriptionally inert, salicylate-induced HSF was undertaken to potentially identify components of the heat shock response that are necessary for full transcriptional induction. Like thermal stress, exposure of HeLa cells to salicylate led to the induction of HSF1 into a DNA-bound state. Despite continued exposure of cells to salicylate, HSF1.DNA binding attenuated much more rapidly than a continuous heat shock. Western blot analysis revealed that the salicylate-induced form of HSF1 was not hyperphosphorylated like the heat-induced form. Furthermore, supershifts of the HSF1 bound to an heat shock element (HSE) oligonucleotide by monoclonal antibodies to phosphoamino acids revealed that salicylate induced threonine phosphorylation of HSF1, whereas heat led to a predominance of HSF1 serine phosphorylation. These data suggest that salicylate-independent signals are necessary to convert HSF1 into a transactivator of heat shock gene expression and that brief acquisition of DNA binding by this factor is insufficient to maximally enhance transcription.

Blotting, Western↗
PubMed1995

Pharmacological modulation of heat shock factor 1 by antiinflammatory drugs results in protection against stress-induced cellular damage.

The activation of heat shock genes by diverse forms of environmental and physiological stress has been implicated in a number of human diseases, including ischemic damage, reperfusion injury, infection, neurodegeneration, and inflammation. The enhanced levels of heat shock proteins and molecular chaperones have broad cytoprotective effects against acute lethal exposures to stress. Here, we show that the potent antiinflammatory drug indomethacin activates the DNA-binding activity of human heat shock transcription factor 1 (HSF1). Perhaps relevant to its pharmacological use, indomethacin pretreatment lowers the temperature threshold of HSF1 activation, such that a complete heat shock response can be attained at temperatures that are by themselves insufficient. The synergistic effect of indomethacin and elevated temperature is biologically relevant and results in the protection of cells against exposure to cytotoxic conditions.

DNA-Binding Proteins↗
PubMed1994

Arachidonate is a potent modulator of human heat shock gene transcription.

Cell and tissue injury activate the inflammatory response through the action(s) of arachidonic acid and its metabolites, leading to the expression of acute-phase proteins and inflammatory cytokines. At the molecular level, little is known how arachidonic acid regulates the inflammatory response. As inflammation is also associated with local increase in tissue temperatures, we examined whether arachidonic acid was directly involved in the heat shock response. Extracellular exposure to arachidonic acid induced heat shock gene transcription in a dose-dependent manner via acquisition of DNA-binding activity and phosphorylation of heat shock factor 1 (HSF1). In addition, exposure of cells to low concentrations of arachidonic acid, which by themselves did not induce HSF1 DNA-binding activity, reduced the temperature threshold for HSF1 activation from elevated temperatures which are not physiologically relevant (> 42 degrees C) to temperatures which can be attained during the febrile response (39-40 degrees C). These results indicate that elevated heat shock gene expression is a direct consequence of an arachidonic acid-mediated cellular response.

Arachidonic Acid↗
PubMed1992

Effect of sodium salicylate on the human heat shock response.

Sodium salicylate, an anti-inflammatory agent, was examined for its effects on the heat shock response in cultured human cells. Salicylate activation of DNA binding by the heat shock transcription factor (HSF) was comparable to activation attained during heat shock. However, sodium salicylate did not induce heat shock gene transcription even though the HSF was bound in vivo to the heat shock elements upstream of the heat shock protein 70 (Hsp 70) gene. These results reveal that activation of the heat shock transcriptional response is a multistep process. Modulation of extracellular pH augments sensitivity to salicylate-induced activation of HSF.

DNA↗
PubMed1991

Heat shock induces two distinct S6 protein kinase activities in quiescent mammalian fibroblasts.

The regulation of S6 kinase activity was used to monitor perturbations of intracellular signaling activity during heat shock of quiescent murine and human fibroblasts. Previous reports on exponentially growing insect and plant cells had indicated that 40S ribosomal protein S6 is dephosphorylated during heat shock; thus inhibition of S6 kinase activity by heat shock was anticipated in NIH 3T3 fibroblasts and human cells (HeLa, diploid embryonic fibroblasts MRC-5, and skin-derived fibroblasts). Unexpectedly, two distinct S6 protein kinases were activated in quiescent fibroblasts after heat exposure. One of the enzymes was partially purified by sequential column chromatography and was determined to be equivalent to the enzyme activated by serum and other growth factors, referred to here as pp70-S6 protein kinase. The other protein S6 kinase, pp90rsk, was identified by a specific immunoprecipitation assay. Monitoring both enzymatic activities during heat shock revealed a temporal pattern of activation that was reversed when compared to non-stressed, mitogen-stimulated cells. Finally, heat shock stimulated protein S6 phosphorylation in cultured, quiescent mammalian cells. These data demonstrate that specific protein kinases can be activated during heat shock, and that some early mitogenic signals may also participate in the response of cells to physiologic stress.

Animals↗
PubMed1987

Neuroleptic-induced neutropenia in the elderly.

A case reported here of Haloperidol-induced neutropenia demonstrates one of many important drug reactions to which the elderly may be predisposed. Neuroleptics can lead to neutropenia by toxic or immunologic mechanisms, and it is impossible to predict which patients will sustain this potentially life-threatening reaction. Fever and infection may be the only clue to this blood dyscrasias. The diagnosis of drug-induced neutropenia is largely one of exclusion coupled with the observation of increasing neutrophil counts after cessation of the drug.

Aged↗