Protection of heat induced cytoxicity by glycerol

Lin, Peck‐Sun; Kwock, Lester; Hefter, K.

doi:10.1002/jcp.1041080318

Cited by 21 publications

(10 citation statements)

References 20 publications

(6 reference statements)

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“…For example, a number of low molecular weight compounds, including glycerol, dimethylsulfoxide (DMSO) and the cellular osmolyte trimethylamine N-oxide (TMAO) have been shown to protect proteins from thermal denaturation and aggregation in vitro (Gerlsma and Stuur, 1972;Back et al, 1979;Gekko and Koga, 1983). In addition, glycerol treatment protects cells from heatinduced cytotoxicity, probably by reducing the extent of protein denaturation (Lin et al, 1981;Henle et al, 1983;Edington et al, 1989). Consequently, we examined whether the addition of these different protein-stabilizing agents to cells persistently infected with the scrapie prion protein (e.g.…”

Section: Introductionmentioning

confidence: 99%

Chemical chaperones interfere with the formation of scrapie prion protein.

1996

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The fundamental event in prion diseases involves a conformational change in one or more of the alpha‐helices of the cellular prion protein (PrP(C)) as they are converted into beta‐sheets during the formation of the pathogenic isoform (PrP(Sc)). Here, we show that exposure of scrapie‐infected mouse neuroblastoma (ScN2a) cells to reagents known to stabilize proteins in their native conformation reduced the rate and extent of PrP(Sc) formation. Such reagents include the cellular osmolytes glycerol and trimethylamine N‐oxide (TMAO) and the organic solvent dimethylsulfoxide (DMSO), which we refer to as ‘chemical chaperones’ because of their influence on protein folding. Although the chemical chaperones did not appear to affect the existing population of PrP(Sc) molecules in ScN2a cells, they did interfere with the formation of PrP(Sc) from newly synthesized PrP(C). We suggest that the chemical chaperones act to stabilize the alpha‐helical conformation of PrP(C) and thereby prevent the protein from undergoing a conformational change to produce PrP(Sc). These observations provide further support for the idea that prions arise due to a change in protein conformation and reveal potential strategies for preventing PrP(Sc) formation.

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Section: Introductionmentioning

confidence: 99%

Chemical chaperones interfere with the formation of scrapie prion protein.

1996

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“…Representative compounds include polyols such as glycerol, solvents such as DMSO, and deuterated water (D 2 O) 1 . In addition to their effects in vitro, some of these compounds appear to influence protein folding and/or stability in vivo (4)(5)(6). Animal cells incubated in the presence of either deuterated water or glycerol, for example, can withstand severe heat shock treatments that would otherwise be lethal to the cells.…”

Section: Introductionmentioning

confidence: 99%

Correcting temperature-sensitive protein folding defects.

Brown¹,

Hong-Brown²,

Welch³

1997

J. Clin. Invest.

173

108

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Recently, we found that different low molecular weight compounds, all known to stabilize proteins in their native conformation, are effective in correcting the temperaturesensitive protein folding defect associated with the ⌬ F508 cystic fibrosis transmembrane regulator (CFTR) protein.Here we examined whether the folding of other proteins which exhibit temperature-sensitive folding defects also could be corrected via a similar strategy. Cell lines expressing temperature-sensitive mutants of the tumor suppressor protein p53, the viral oncogene protein pp60 src , or a ubiquitin activating enzyme E1, were incubated at the nonpermissive temperature (39.5 Њ C) in the presence of glycerol, trimethylamine N -oxide or deuterated water. In each case, the cells exhibited phenotypes similar to those observed when the cells were incubated at the permissive temperature (32.5 Њ C), indicative that the particular protein folding defect had been corrected. These observations, coupled with our earlier work and much older studies in yeast and bacteria, indicate that protein stabilizing agents are effective in vivo for correcting protein folding abnormalities. We suggest that this type of approach may prove to be useful for correcting certain protein folding abnormalities associated with human diseases. (

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“…However, several other reports have indicated that the 1,10-phenanthroline does affect the cell growth inhibitory or DNA damaging properties of bleomycin [33][34][35]. The relatively membraneimpermeant Fe 3+ chelators diethylenediaminepentaacetic acid and deferoxamine were reported to have no effect on bleomycin cytotoxicity [36]. It has also been reported that the cytotoxic effects of bleomycin on pulmonary artery endothelial cells were reduced by deferoxamine, but not by EDTA [37].…”

Section: Discussionmentioning

confidence: 97%

“…Previous studies in cell systems employing either chelating agents or iron-deficient growth media to deplete iron are mixed in their conclusions regarding the requirement for iron in bleomycin growth inhibitory activity [32][33][34][35][36][37]. HL-60 cells grown in iron-depleted medium displayed a decrease in bleomycin-mediated growth inhibition and DNA damage [38].…”

Section: Discussionmentioning

confidence: 98%