Pharmacological induction of Hsp70 protects apoptosis-prone cells from doxorubicin: comparison with caspase-inhibitor- and cycle-arrest-mediated cytoprotection

Demidenko, Zoya N.; Vivo, Claire; Halicka, H. Dorota; Li, C. J.; Bhalla, Kapil N.; Broude, Eugenia V.; Mv, Blagosklonny

doi:10.1038/sj.cdd.4401812

Cited by 75 publications

(71 citation statements)

References 36 publications

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“…Levels of SGT1, Chp1, HSP90, and HSP40 proteins remained essentially unchanged. As expected, the presence of GA increased the basal levels of HSP70 protein (25). GA treatment also destabilized RIP2 and Skp1A.…”

Section: Hsp90 But Not Sgt1 Controls Nod1 Stabilitymentioning

confidence: 59%

SGT1 is essential for Nod1 activation

Correia

Miranda

Leonard

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

134

126

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The Nod-like receptor family in man contains proteins that recognize invasive bacteria. Nod1, a member of this family, is activated by specific peptidoglycan-derived muropeptides that contain meso-diaminopimelic acid. Plants contain a large family of proteins known as resistance (R) proteins that have common structural features with the Nod-like receptors and are essential for protection against a variety of plant pathogens. Extensive genetic studies have shown that the R protein function is determined by multiple proteins including SGT1, Rar1, and HSP90. Here we show that SGT1 positively regulates Nod1 activation. Depletion of SGT1 with siRNA did not affect stability of Nod1 protein or of downstream signaling molecules but did prevent multiple cellular responses associated with Nod1 activation. In contrast, depletion of the mammalian orthologue of Rar1, Chp1, had no effect on Nod1-dependent cellular activation. Finally, depletion of HSP90 or addition of a pharmacologic inhibitor of HSP90 resulted in loss of Nod1 protein. Thus, we show common regulatory pathways in plant R protein and human Nod1-dependent pathways and provide the basis for understanding the Nod1 pathway.Chp1 ͉ HSP90 ͉ SIP ͉ Nod2 ͉ Nod-like receptors

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Section: Hsp90 But Not Sgt1 Controls Nod1 Stabilitymentioning

confidence: 59%

SGT1 is essential for Nod1 activation

Correia

Miranda

Leonard

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

134

126

View full text Add to dashboard Cite

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“…Cell survival after radiation was determined using an MTT assay as previously described (10). In brief, 2x10 4 cells were plated in 200 µl culture medium in 96-well plates and incubated for 48 h. At the indicated time points (2,24,48 and 72 h after radiation), a total of 20 µl MTT (Sigma-Aldrich) solution in phosphate-buffered saline was added to each well.…”

Section: Methodsmentioning

confidence: 99%

Protective effects of acteoside against X-ray-induced damage in human skin fibroblasts

Yang

Yao

Liu

et al. 2015

Molecular Medicine Reports

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Abstract. To investigate the protective effects of acteoside against apoptosis induced by X-ray radiation in human skin fibroblasts (HSFs), the cells were divided into the following groups: Control group; X-ray radiation group; acteoside group, in which the confluent cells were preincubated with 50 µg/ml acteoside for 2 h followed by radiation; and positive control group, in which the cells were preincubated with 50 µg/ml paeoniflorin followed by radiation. For the radiation, HSF cells preincubated with acteoside or paeoniflorin were exposed to X-ray beams at a dose-rate of 3 Gy/min (16 Gy in total). Cell viability, apoptosis and intracellular alteration of redox were monitored by MTT and flow cytometry. Compared with the radiation group, the number of cells arrested at the G0/G1 phase was significantly reduced in the acteoside and paeoniflorin groups, respectively (P<0.05). X-ray radiation induced marked apoptosis in HSF cells and acteoside reversed this effect. Compared with the radiation group, the generation of intracellular reactive oxygen species (ROS) was abrogated by pre-incubation with acteoside or paeoniflorin (P<0.05). In addition, the upregulation of pro-caspase-3 induced by radiation was reversed by acteoside or paeoniflorin. Radiation could induce upregulation of Bax and downregulation of Bcl-2; however, it was reversed completely after administration of acteoside or paeoniflorin. Furthermore, the enhanced expression of ERK and JNK induced by radiation was reversed by acteoside or paeoniflorin. Acteoside could protect the cells from X-ray induced damage through enhancing the scavenging activity of ROS, decreasing the Bax/Bcl-2 ratio and downregulating the activity of procaspase-3, as well as modulating the mitogen-activated protein kinase signaling pathways.

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“…Ansamycins have been shown to cause cell cycle arrest (McIlwrath et al, 1996;Kim et al, 1999;Srethapakdi et al, 2000;Hostein et al, 2001;de Ca´rcer, 2004;Georgakis et al, 2006a) and apoptosis (Munster et al, 2002;Demidenko et al, 2006;Georgakis et al, 2006b). Targeting the cell cycle machinery is a novel strategy used in cancer therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Hsp90 function by ansamycins causes downregulation of cdc2 and cdc25c and G2/M arrest in glioblastoma cell lines

et al. 2007

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Ansamycins exert their effects by binding heat shock protein 90 (Hsp90) and targeting important signalling molecules for degradation via the proteasome pathway. We wanted to study the effect of geldanamycin (GA) and its derivative 17-allylamino-17-demethoxygeldanamycin (17-AAG) on glioblastoma cell lines. We show that these cells are growth inhibited by ansamycins by being arrested in G 2 / M and, subsequently, cells undergo apoptosis. The protein levels of cell division cycle 2 (cdc2) kinase and cell division cycle 25c (cdc25c) were downregulated upon GA and 17-AAG treatment and cdc2 kinase activity was inhibited. However, other proteins involved in the G 2 /M checkpoint were not affected. The cdc2 and cdc25c mRNA levels did not show significant differences upon ansamycin treatment, but the stability of cdc2 protein was reduced. The association of cdc2 and cdc25c with p50 cdc37 , an Hsp90 cochaperone, decreased, but the interaction of cdc2 and cdc25c with the Hsp70 co-chaperone increased after ansamycin treatment. Proteasome inhibitors were able to rescue the cdc2 downregulation, but not the cdc25c reduction. However, calpain inhibitors were able to rescue the cdc25c downregulation, suggesting that cdc25c is proteolysed by calpains in the presence of ansamycins, and not by the proteasome. We conclude that ansamycins downregulate cdc2 and cdc25c by two different mechanisms.

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Pharmacological induction of Hsp70 protects apoptosis-prone cells from doxorubicin: comparison with caspase-inhibitor- and cycle-arrest-mediated cytoprotection

Cited by 75 publications

References 36 publications

SGT1 is essential for Nod1 activation

SGT1 is essential for Nod1 activation

Protective effects of acteoside against X-ray-induced damage in human skin fibroblasts

Inhibition of Hsp90 function by ansamycins causes downregulation of cdc2 and cdc25c and G2/M arrest in glioblastoma cell lines

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