Biomedical subjects

Seunath A Khalawan

Publications and source records attributed to Seunath A Khalawan.

3 recordsLinked to original sources

PubMed2000

Dioctyl phthalate increases the percentage of unsaturated fatty acids with a concomitant decrease in cellular heat shock sensitivity in the yeast Saccharomyces cerevisiae.

In the past it has been reproducibly demonstrated that 37 degrees C-grown DBY747 yeast cells have 29% more unsaturated fatty acids and a 3 degrees C higher maximal heat shock response (HSR) than their 25 degrees C counterparts. Suddenly the HSR and lipid profiles of cells grown at 25 degrees C and 37 degrees C became indistinguishable from one another. This paper reports an aberrantly high level of unsaturated fatty acids and an abnormally insensitive HSR in cells grown at 25 degrees C in yeast nitrogen base (YNB) that has been reconstituted from dehydrated medium packaged in 'new' plastic containers. Effective even at a 1:600 dilution of reconstituted medium in laboratory-made YNB, the 'active ingredient' was identified using a combination of HPLC and mass spectroscopy as dioctyl phthalate (a plasticising agent). Furthermore, the same levels of increase in the percentage of unsaturated fatty acids and decrease in the sensitivity of HSR were found in cells grown in laboratory-made YNB that contained as little as 36 microM pure dioctyl phthalate. This compound nevertheless failed to elicit an observable effect on cellular growth rate at levels up to and including 144 microM. These results suggest that dioctyl phthalate causes yeast cells to accumulate high levels of unsaturated fatty acids with a concomitant decrease in the sensitivity of the HSR, without compromising overall cellular function. They also support earlier work that suggested that the HSR is exquisitely sensitive to the level of unsaturated fatty acids present in yeast cells.

Chromatography, High Pressure Liquid↗

PubMed2000

Cellular lipid composition influences stress activation of the yeast general stress response element (STRE).

The heat inducibility of the yeast heat-shock response (HSR) pathway has been shown to be critically dependent on the level of unsaturated fatty acids present in the cell. Here the inducibility by heat or salt of the independently regulated general stress response (GSR) pathway is shown to be affected in the same way. An increase in the percentage of unsaturated fatty acids in heat- or salt-acclimated cells correlated with a decrease in the induction of a general stress-response-promoter-element (STRE)-driven reporter gene by either stress. Despite inducing reporter gene expression, sorbic acid treatment did not confer salt cross-tolerance on the cells. This failure correlated with a failure to increase the percentage of unsaturated fatty acids in the cells, suggesting that GSR pathway induction, in the absence of lipid changes, is insufficient for the induction of cross-tolerance. Cells grown with fatty acid supplements under anaerobic conditions provided further evidence for a potential role for lipids in the acquisition of stress resistance. These cells contained different fatty acid profiles depending on the fatty acid supplement supplied, exhibited differential sensitivity to both heat and salt stress, but had not undergone STRE induction. These results suggest that heat- and salt-stress induction of the GSR are sensitive to the level of unsaturated fatty acids present in the cell and that stress cross-tolerance may be a lipid-mediated phenomenon. Given that an increased level of unsaturated fatty acids also down-regulates heat induction of the HSR pathway, these observations lead to the provocative hypothesis that lipid modifications, rather than HSR or GSR pathway induction, are a major contributor to the induced heat and salt tolerance of yeast cells.

Adaptation, Biological↗

PubMed1997

Alterations in cellular lipids may be responsible for the transient nature of the yeast heat shock response.

The stress-sensing systems leading to the cellular heat shock response (HSR) and the mechanism responsible for the desensitizing of this response in stress-acclimated cells are largely unknown. Here it is demonstrated that there is a close correlation between a 3 degrees C increase in the temperature required for maximal activation of a heat-shock (HS)-inducible gene in Saccharomyces cerevisiae and an increase in the percentage of cellular unsaturated fatty acids when cells are subjected to extended periods of growth at 37 degrees C. The latter occurs with the same kinetics as HS gene down-regulation during a prolonged HS and is reversed by reacclimation to growth at 25 degrees C. The transient nature of the HS may therefore be due to a lipid-mediated decrease in cellular heat sensitivity. Further evidence that unsaturated fatty acids desensitize cells to heat, with a resultant down-regulation of the HSR, is provided by demonstrating a 9 degrees C increase in the temperature required for maximal induction of this HS-inducible gene in cells containing high levels of unsaturated fatty acids assimilated during anaerobic growth at 25 degrees C.

Aerobiosis↗