Heat Shock Is Lethal to Fibroblasts Microinjected with Antibodies Against hsp70

Riabowol, Karl; Mizzen, Lee; Welch, William J.

doi:10.1126/science.3175665

Cited by 595 publications

(224 citation statements)

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“…HSP70 is the most prominent protein induced by a variety of stress conditions in all cells investigated (Schlesinger, 1990;Pelham, 1990 (Li & Laszlo, 1985;Riabowol et al, 1988;Johnston & Kucey, 1988). Most recently, it has been shown that cells transfected with hsp70 governed by a constitutive promoter were more resistant to heat-shock, directly supporting the above notion (Angelidis et al, 1991;Li et al, 1991).…”

Section: Discussionmentioning

confidence: 53%

Induction of HSP70 is associated with vincristine resistance in heat-shocked 9L rat brain tumour cells

Lee¹,

Lin²,

Chen³

et al. 1992

Br J Cancer

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SummaryThe most prominent cellular changes in heat-shock response are induction of HSPs synthesis and reorganisation of cytoskeleton. Vincristine was used as a tool to evaluate the integrity of microtubules in 9L rat brain tumour cells recovering from heat-shock treatment. Cells treated at 45°C for 15 min and recovered under normal growing condition became resistant to vincristine-inflicted cytotoxicity and microtubule destruction. Among all HSPs, the level of HSP70 and the degree of vincristine resistance are best correlated. HSP70and tubulin were found to be associated with each other as they were co-immunoprecipitated by either anti-HSP70 or anti-p-tubulin monoclonal antibody. The current studies establish for the first time that HSP70can complex with tubulin in cells and this association may stabilise the organisation of microtubules thus protect the heat-treated cells from vincristine damage. These findings are noteworthy in combining hyperthermia and chemotherapy in the management of malignant diseases.Heat-shock proteins (HSPs) are a small set of proteins induced in cells subjected to supraoptimal temperature and other related physiological stresses (Lindquist & Craig, 1988;Schlesinger, 1990;Schlesinger et al., 1990; Morimoto et al., 1990). The synthesis of HSPs is suggested to be related to the development of thermotolerance in cells that survived the initial heat-treatment (Li & Mak, 1985;Hahn & Li, 1990;Black & Subjeck, 1990). The HSPs are highly conservative and usually termed by their apparent molecular weights. Three classes of major HSPs, i.e., HSPl10, 90 and 70 are commonly detected in mammalian cells (Lindquist & Craig, 1988). HSP70 exists as a family in most organisms and has been the most extensively studied. In rodent cells, this family consists of two closely related proteins (>80% homology at the amino acid level) which have been known as the constitutive form of HSP70 (also known as HSC70, designated as HSP72 hereafter because of its slightly higher molecular weight) and the inducible form of HSP70 (designated as the HSP70 hereafter) (Hightower & White, 1981;Lee et al., 1991). HSP72 is slightly heat inducible, constitutively expressed and found at higher levels in growing cells than in resting cells (Pelham, 1986). This protein was found to be multifunctional. It functions as clathrin uncoating ATPase (Chappell et al., 1986;Deluca-Flaherty et al., 1990) and as molecular chaperone that binds to nascent polypeptides and maintains them in unfolded states, to facilitate their intracellular translocation (Deshaies et al., 1988;Chirico et al., 1988) and/or to accelerate their proper folding and oligomerisation (Beckmann et al., 1990;Pelham, 1990). Recently, HSP72 has been shown to be involved the in vivo assembly of microtubules (Gupta, 1990). On the other hand, HSP70 is highly heat inducible and hardly detectable under normal conditions. Its function is suggested to be similar to that of HSP72 because of the high degree of homology between these two proteins (Lindquist & Craig, 1988). In additi...

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Section: Discussionmentioning

confidence: 53%

Induction of HSP70 is associated with vincristine resistance in heat-shocked 9L rat brain tumour cells

Lee¹,

Lin²,

Chen³

et al. 1992

Br J Cancer

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“…They indicated a concomitant increase in major heat-shock pro teins, especiallly hsp70. A strong line of evidence of the role for hsp70 in induced tolerance has been shown by Riabowol et al (1988) when they demon strated that heat shock is lethal to fibroblasts if they were injected with antibody to hsp70. Their result was further reinforced by the fact that competitive inhibition of hsp70 gene expression causes ther mosensitivity in the Chinese hamster ovary cell line (Johnston and Kucey, 1988).…”

Section: Discussionmentioning

confidence: 97%

Induced Tolerance to Ischemia in Gerbil Hippocampal Neurons

Kirino

Tsujita

Tamura

1991

J Cereb Blood Flow Metab

565

216

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Summary: Brief ischemia induced tolerance to subse quent ischemia in the hippocampal neurons. Male Mon golian gerbils were subjected to 2 min of ischemia in an awake condition. This ischemic insult only rarely pro duced neuronal damage in the gerbil brain. One day (n = 9), 2 days (n = 9), or 4 days (n = 10) following the first brief ischemia, the animals (double-ischemia group) were subjected to the second ischemia for 5 min. The single ischemia group received a sham procedure instead of the first ischemia and was identically subjected to the second ischemia I day (n = 9), 2 days (n = 10), and 4 days (n = 13) following the sham procedure. One week following the second ischemia, all gerbils were perfusion fixed and the neuronal density in the hippocampal CA I sector was measured. In double-ischemia groups, the neuronal denThe brain is particularly vulnerable to distur bances of energy metabolism, such as ischemia, an oxia, hypoglycemia, or status epilepticus (Auer and Siesj6, 1988; Siesj6 and Bengtsson, 1989). Even a brief episode of ischemia destroys certain groups of ischemia-sensitive neurons. These selectively vul nerable neurons are found in the hippocampal CA 1 sector, in the dorsolateral striatum, in certain layers of the cerebral cortex, and in the cerebellar cortex (Wieloch, 1985). Among these vulnerable cells in the brain, hippocampal CAl pyramidal cells have been the most extensively studied. Following brief ischemia, CA 1 pyramidal cells recover energy me tabolism (Pulsinelli and Duffy, 1983; Arai et a!. , 1986) and electrophysiological activity (Suzuki et a!., 1983). The fine structure of CA 1 pyramidal cells is maintained well until they are disintegrated 3 or 4Received July 18 , 1990 ; revised August 27 , 1990 ; accepted Au gust 31 , 1990 .Ad dress correspondence and reprint requests to Dr . T . Kirino at Department of Neurosurgery , Teikyo University School of Medicine , 7-3-\ Kaga , It abashi-ku , Tokyo 173 , Japan .Abbreviation used: hsp70 , 70-kDa heat-shock protein . 299sity per I-mm length of the pyramidal cell layer was 103.4 ± 93. 1 (SD) in the I-day subgroup, 125. 6 ± 64. 2 in the 2-day subgroup, and 176. 2 ± 93.7 in the 4-day subgroup, while the density in normal gerbils was 254.7 ± 18.6. The average neuronal density in the single-ischemia group was much lower than that in the double-ischemia group (whole control group: 10. 9 ± 27.4). Immunostaining using monoclonal antibody raised against 70-kDa heat-shock protein revealed an increase in 70-kDa heat-shock protein in the CAl area following 2 min of ischemia. Very brief ischemia induces heat-shock proteins and, presumably, thereby renders neurons more tolerant to subsequent metabolic stress.

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“…Pelham (1986) has shown that HSP70 proteins bind to partially dena tured proteins and prevent further loss of, tertiary structure of these proteins. Riabowol et al (1988) found that heat shock is lethal to fibroblasts micro injected with antibodies against HSP70 protein. In recent reports, moreover, sublethal ischemia suffi cient to induce HSP70 proteins protects brain cells against subsequent cerebral ischemia (Kirino et aI., 1991;Kitagawa et aI., 199 1;Liu et aI., 1992).…”

Section: Function Of Hsp70 Proteinmentioning

confidence: 99%