Hsp27 Inhibits Cytochrome <i>c</i>-Mediated Caspase Activation by Sequestering Both Pro-caspase-3 and Cytochrome <i>c</i>

Concannon, Caoimhín G.; Orrenius, Sten; Samali, Afshin

doi:10.3727/000000001783992605

Cited by 203 publications

(156 citation statements)

References 27 publications

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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%

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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Section: Discussionmentioning

confidence: 99%

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

Baker

Roy

Brandon

et al. 2014

JARO

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“…Hsp27 has been reported to interact with caspase-3, thereby inhibiting caspase-3 activation (26). Cells treated with OGX-427 expressed significantly higher amounts of cleaved caspase-3 and poly(ADP-ribose) polymerase products compared with cells treated with control ODN (Fig.…”

Section: Ogx-427^induced Hsp27 Knockdown Increases Apoptotic Rates Inmentioning

confidence: 97%

“…Hsp27 prevents the formation of the apoptosome by either preventing the release of mitochondrial cytochrome c or directly sequestering cytochrome c in the cytosol after mitochondrial release (31). Hsp27 also directly interacts with and inhibits caspase-3 activation (26). Hsp27 can interfere with the extrinsic cell death pathway by inhibiting Daxx, a mediator of Fas-induced caspase-independent apoptosis (32).…”

Section: Discussionmentioning

confidence: 99%

Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells

Kamada

Muramaki

et al. 2007

Molecular Cancer Therapeutics

174

140

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“…HSP27 can interfere with an apoptotic signal transduction at several steps. It is implicated in preserving mitochondrial integrity and reducing cytochrome c release (49); it can bind directly to cytochrome c, thus preventing activation of procaspase-9 (4,7,20); and it can bind to procaspase-3 and inhibit its activation (7,44) (Fig. 2).…”

Section: Hsps Control Apoptotic Signaling Pathwaysmentioning

confidence: 99%

Invited Review: Interplay between molecular chaperones and signaling pathways in survival of heat shock

Gabai

Sherman

2002

Journal of Applied Physiology

158

109

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. Invited Review: Interplay between molecular chaperones and signaling pathways in survival of heat shock. J Appl Physiol 92: 1743-1748, 2002; 10.1152/ japplphysiol.01101.2001.-Heat shock of mammalian cells causes protein damage and activates a number of signaling pathways. Some of these pathways enhance the ability of cells to survive heat shock, e.g., induction of molecular chaperones [heat shock protein (HSP) HSP72 and HSP27], activation of the protein kinases extracellular signal-regulated kinase and Akt, and phosphorylation of HSP27. On the other hand, heat shock can activate a stress kinase, c-Jun NH 2-terminal kinase, thus triggering both apoptotic and nonapoptotic cell death programs. Recent data indicate that kinases activated by heat shock can regulate synthesis and functioning of the molecular chaperones, and these chaperones modulate activity of the cell death and survival pathways. Therefore, the overall balance of the pathways and their interplay determine whether a cell exposed to heat shock will die or survive and become stress tolerant. thermotolerance; heat shock proteins; mitogen-activated protein kinases; apoptosis EXPOSURE OF MAMMALIAN CELLS to elevated temperatures (heat shock) triggers several signaling pathways, some that facilitate cell survival and some that initiate cell death programs. The outcome of a cell's exposure to heat shock may be either a development of a state of tolerance to heat shock and other stresses, if survival pathways prevail, or cell death, if death pathways prevail. The first-discovered survival pathway activated by heat shock was the heat shock response, i.e., induction of heat shock proteins (HSPs) such as HSP72, HSP27, HSP40, and HSP90, mediated by heat shock transcription factors (HSFs) (see Ref. 46 for a recent review). HSPs confer thermotolerance as well as resistance to other stresses, such as ethanol, heavy metals, oxidative stress, ischemia, or tumor necrosis factor (see Refs. 16 and 23 for review).Heat shock causes extensive denaturation and aggregation of intracellular proteins; therefore, early studies focused on the search of labile critical proteins whose damage when exposed to heat shock may lead to cell death (see Refs. 25 and 26 for review). Among major proteins easily denatured and aggregated in heat-shocked cells were components of nuclear matrix and cytoskeleton (2,25,26,31,41), although it should be noted that there are no data directly linking damage of these proteins to cell death. HSPs serve as molecular chaperones in refolding, disaggregation, and degradation of damaged polypeptides (see Refs. 15 and 21 for review). In fact, aggregation of nuclear proteins as well as a reporter enzyme (firefly luciferase) after heat shock was reduced in thermotolerant cells expressing HSPs, and these cells demonstrated faster solubilization of aggregated proteins during the recovery period (2,26,42,53). Furthermore, expression of HSP72 (the major inducible member of the HSP70 family) alone was sufficient to reduce nuclear protein aggregation and accelera...

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Hsp27 Inhibits Cytochrome c-Mediated Caspase Activation by Sequestering Both Pro-caspase-3 and Cytochrome c

Cited by 203 publications

References 27 publications

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

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

Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells

Invited Review: Interplay between molecular chaperones and signaling pathways in survival of heat shock

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