The hyperfluidization of mammalian cell membranes acts as a signal to initiate the heat shock protein response.
The concentrations of two structurally distinct membrane fluidizers, the local anesthetic benzyl alcohol (BA) and heptanol (HE), were used at concentrations so that their addition to K562 cells caused identical increases in the level of plasma membrane fluidity as tested by 1,6-diphenyl-1,3,5-hexatriene (DPH) anisotropy. The level of membrane fluidization induced by the chemical agents on isolated membranes at such concentrations corresponded to the membrane fluidity increase seen during a thermal shift up to 42 degrees C. The formation of isofluid membrane states in response to the administration of BA or HE resulted in almost identical downshifts in the temperature thresholds of the heat shock response, accompanied by increases in the expression of genes for stress proteins such as heat shock protein (HSP)-70 at the physiological temperature. Similarly to thermal stress, the exposure of the cells to these membrane fluidizers elicited nearly identical increases of cytosolic Ca2+ concentration in both Ca2+-containing and Ca2+-free media and also closely similar extents of increase in mitochondrial hyperpolarization. We obtained no evidence that the activation of heat shock protein expression by membrane fluidizers is induced by a protein-unfolding signal. We suggest, that the increase of fluidity in specific membrane domains, together with subsequent alterations in key cellular events are converted into signal(s) leading to activation of heat shock genes.
Balogh
Gábor
G
Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
Horváth
Ibolya
I
Nagy
Enikõ
E
Hoyk
Zsófia
Z
Benkõ
Sándor
S
Bensaude
Olivier
O
Vígh
László
L
D000779:Anesthetics, Local / Q000494:pharmacology*; D019905:Benzyl Alcohol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D048430:Cell Shape; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D018869:Heat-Shock Response / Q000502:physiology*; D019850:Heptanol / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D020014:K562 Cells; D008560:Membrane Fluidity; D008564:Membrane Potentials / Q000502:physiology; D011489:Protein Denaturation
D000779:Anesthetics, Local; D018840:HSP70 Heat-Shock Proteins; D019850:Heptanol; D019905:Benzyl Alcohol; D002118:Calcium