Hsp70 Inhibits Heat-induced Apoptosis Upstream of Mitochondria by Preventing Bax Translocation

Stankiewicz, Adam R.; Lachapelle, Guillaume; Foo, Cheryl P.Z.; Radicioni, Stefanie M.; Mosser, Dick D.

doi:10.1074/jbc.m509497200

Cited by 388 publications

(321 citation statements)

References 67 publications

(85 reference statements)

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“…A recent report suggests that inhibition of bax translocation to mitochondria by HSP70 is the crucial factor in the cellular decision to either trigger or suppress apoptosis. 25 We have focused on the pro-and anti-apoptotic bcl-2 family members because of their central role in regulating cytochrome c release in stressed cells. We have found that sorbitol treatment increased expression of the bax protein while decreasing the expression of bcl-2 protein.…”

Section: Discussionmentioning

confidence: 99%

Retracted: Heat‐shock pretreatment inhibits sorbitol‐induced apoptosis in K562, U937 and HeLa cells

Marfè

Pucci

Martino

et al. 2009

Intl Journal of Cancer

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The aim of this study was to determine whether heat-shock pretreatment exerted a protective effect against sorbitol-induced apoptotic cell death in K562, U937 and HeLa cell lines and whether such protection was associated with a decreased cytochrome c release from mithocondria and a decreased activation of caspase-9 and -3. Following heat-shock pretreatment (42 6 0.3°C for 1 hr), these cell lines were exposed to sorbitol for 1 hr. Apoptosis was evaluated by DNA fragmentation, whereas caspase-9,-3 activation, cytochrome c release and heat-shock protein70 (HSP70) were assayed by Western Blot. Sorbitol exposure-induced apoptosis in these different cell lines with a marked activation of caspase-9 and caspase-3, whereas heat-shock pretreatment before sorbitol exposure, induced expression of HSP70 and inhibited sorbitol-mediated cytochrome c release and subsequent activation of caspase-9 and caspase-3. Similarly, overexpression of HSP70 in the three cell lines studied prevented caspase-9 cleavage and activation as well as cell death. Furthermore, we showed that the mRNA expression of iNOS decreased during both the heat-shock treatment and heat-shock pretreatment before sorbitol exposure. By contrast, the expression of Cu-Zn superoxide dismutase (SOD) and Mn-SOD proteins increased during heat-shock pretreatment before sorbitol exposure. We conclude that, heat-shock pretreatment protects different cell lines against sorbitol-induced apoptosis through a mechanism that is likely to involve SOD family members. ' 2009 UICC

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Section: Discussionmentioning

confidence: 99%

Retracted: Heat‐shock pretreatment inhibits sorbitol‐induced apoptosis in K562, U937 and HeLa cells

Marfè

Pucci

Martino

et al. 2009

Intl Journal of Cancer

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“…finding, as an antiapoptotic role for this protein has been recently described (Stankiewicz et al, 2005). Some common genes for both concentrations of docetaxel included DCT, TYR, TYRP1 and MAF.…”

Section: Molecular Profiling Of Docetaxel Cytotoxicity H Hernández-vamentioning

confidence: 82%

Molecular profiling of docetaxel cytotoxicity in breast cancer cells: uncoupling of aberrant mitosis and apoptosis

2006

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Among microtubule-targeting agents, docetaxel has received recent interest owing to its good therapeutic index. Clinical trials have underlined its potential for the treatment of advanced breast cancer, although little is known about its molecular mode of action in this context. We characterized the molecular changes induced by docetaxel in two well-known human breast carcinoma cell lines. Two mechanisms of action according to drug concentration were suggested by a biphasic sensitivity curve, and were further validated by cell morphology, cell cycle and cell death changes. Two to four nanomolar docetaxel induced aberrant mitosis followed by late necrosis, and 100 nM docetaxel induced mitotic arrest followed by apoptosis. Passing through mitosis phase was a requirement for hypodiploidy to occur, as shown by functional studies in synchronized cells and by combining docetaxel with the proteasome inhibitor MG132. Transcriptional profiling showed differences according to cell line and docetaxel concentration, with cell cycle, cell death and structural genes commonly regulated in both cell lines. Although p53 targets were mainly induced with low concentration of drug in MCF7 cells, its relevance in the dual mechanism of docetaxel cytotoxicity was ruled out by using an isogenic shp53 cell line. Many of the genes shown in this study may contribute to the dual mechanism by which docetaxel inhibits the growth of breast cancer cells at different concentrations. These findings provide a basis for rationally enhancing docetaxel therapy, considering lower concentrations, and better drug combinations.

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“…The protection conferred by HSPs is not limited to these "chaperone" activities; HSPs also inhibit lipid peroxidation and oxidative damage to DNA (Park et al 1998;Su et al 1999;Martindale and Holbrook 2002). In addition, HSPs have been shown to inhibit multiple pro-apoptotic signaling events (Jaattela et al 1998;Beere et al 2000;Pandey et al 2000a, b;Concannon et al 2001Concannon et al , 2003Tsuchiya et al 2003;Stankiewicz et al 2005;Rodina et al 2007;Jiang et al 2009;Evans et al 2010;Pasupuleti et al 2010). HO-1 is a heat shock-inducible protein that lacks intrinsic chaperone activity; however, it inhibits oxidative stress, inflammation, and apoptosis in multiple tissue types (Kirkby and Adin 2006;Ryter et al 2006;Gozzelino et al 2010;Paine et al 2010;Blancou et al 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Stress-induced HSP70 inhibits apoptotic cell death in a large number of systems. HSP70 inhibits multiple pro-apoptotic signals, including oligomerization of Bax, release of both cytochrome c and second mitochondria-derived activator of caspases (Smac) from mitochondria, formation of a functional apoptosome, and even cell death subsequent to caspase 3 activation (Jaattela et al 1998;Beere et al 2000;Tsuchiya et al 2003;Stankiewicz et al 2005;Jiang et al 2009;Evans et al 2010). Moreover, HSP70 inhibits aminoglycosideinduced hair cell death in vitro and hearing loss in vivo (Taleb et al 2008(Taleb et al , 2009May et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

Baker

Roy

Brandon

et al. 2014

JARO

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Cisplatin is a highly successful and widely used chemotherapy for the treatment of various solid malignancies in both adult and pediatric patients. Side effects of cisplatin treatment include nephrotoxicity and ototoxicity. Cisplatin ototoxicity results from damage to and death of cells in the inner ear, including sensory hair cells. We showed previously that heat shock inhibits cisplatin-induced hair cell death in whole-organ cultures of utricles from adult mice. Since heat shock protein 70 (HSP70) is the most upregulated HSP in response to heat shock, we investigated the role of HSP70 as a potential protectant against cisplatin-induced hair cell death. Our data using utricles from HSP70 −/− mice indicate that HSP70 is necessary for the protective effect of heat shock against cisplatin-induced hair cell death. In addition, constitutive expression of inducible HSP70 offered modest protection against cisplatin-induced hair cell death. We also examined a second heat-inducible protein, heme oxygenase-1 (HO-1, also called HSP32). HO-1 is an enzyme responsible for the catabolism of free heme. We previously showed that induction of HO-1 using cobalt protoporphyrin IX (CoPPIX) inhibits aminoglycoside-induced hair cell death. Here, we show that HO-1 also offers significant protection against cisplatin-induced hair cell death. HO-1 induction occurred primarily in resident macrophages, with no detectable expression in hair cells or supporting cells. Depletion of macrophages from utricles abolished the protective effect of HO-1 induction. Together, our data indicate that HSP induction protects against cisplatin-induced hair cell death, and they suggest that resident macrophages mediate the protective effect of HO-1 induction.

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Hsp70 Inhibits Heat-induced Apoptosis Upstream of Mitochondria by Preventing Bax Translocation

Cited by 388 publications

References 67 publications

Retracted: Heat‐shock pretreatment inhibits sorbitol‐induced apoptosis in K562, U937 and HeLa cells

Retracted: Heat‐shock pretreatment inhibits sorbitol‐induced apoptosis in K562, U937 and HeLa cells

Molecular profiling of docetaxel cytotoxicity in breast cancer cells: uncoupling of aberrant mitosis and apoptosis

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

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