Use of Hsf1−/− mice reveals an essential role for HSF1 to protect lung against cadmium-induced injury

Wirth, Delphine; Christians, Elisabeth; Li, Xiang; Benjamin, Ivor J.; Gustin, Pascal

doi:10.1016/s0041-008x(03)00256-4

Cited by 26 publications

(17 citation statements)

References 37 publications

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“…HSF1 knockdown increased cadmium-mediated cytotoxicity, so HSP70 induction via the activation of HSF1 is a cytoprotective response to cadmium. Consistent with this, HSF1/HSP70 has been found to have a protective function in in vivo experiments using HSF1 knockout mice (Wirth et al, 2003).…”

Section: Discussionsupporting

confidence: 68%

Cadmium-mediated activation of the HSP90/HSF1 pathway regulated by reactive persulfides/polysulfides

Shinkai

Masuda

Akiyama³

et al. 2017

Toxicol. Sci.

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Cadmium is an environmental electrophile that modifies reactive thiols in proteins, indicating that this heavy metal may modulate redox-signal transduction pathways. The current consensus is that reactive persulfides and polysulfides produced by cystathionine c-lyase (CSE) and cystathionine b-synthase are highly nucleophilic and thus cadmium may be captured by these reactive sulfur species. It has previously been found that electrophile-mediated covalent modifications of the heat shock protein (HSP) are involved in the activation of heat shock factor 1 (HSF1) pathway. The effects of cadmium on the activation of HSP/HSF1 pathway were investigated in this study. Exposure of bovine aortic endothelial cells to cadmium resulted in modification of HSP90 and HSF1 activation, thereby up-regulating the downstream protein HSP70. The siRNA-mediated knockdown of HSF1 enhanced the cytotoxicity induced by cadmium, suggesting that the HSP90/HSF1 pathway contributes to protection against cadmium toxicity. The knockdown of CSE and/or cystathionine b-synthase decreased the levels of reactive sulfur species in the cells and increased the degree of HSP70 induction and cytotoxicity caused by exposure to cadmium. Overexpression of CSE diminished cadmium-mediated up-regulation of HSP70 and cytotoxicity. These results suggest that cadmium activates HSF1 by modifying HSP90 and that reactive sulfur species regulate the redox signal transduction pathway presumably via capture of cadmium, resulting in protection against cadmium toxicity under toxic conditions.

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Section: Discussionsupporting

confidence: 68%

Cadmium-mediated activation of the HSP90/HSF1 pathway regulated by reactive persulfides/polysulfides

Shinkai

Masuda

Akiyama³

et al. 2017

Toxicol. Sci.

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“…A similar preconditioning phenomenon has also been reported in other tissues, including the spinal cord and periphery (Sawynok and Liu, 2003), lung (Rivo et al, 2004a(Rivo et al, , 2004bSoncul et al, 1999;Wirth et al, 2003), liver (Nakayama et al, 1999;Lee and Emala, 2000;Peralta et al, 1998Peralta et al, , 1999, and kidney (Yamasowa et al, 2005). The hormetic-like biphasic dose is also independent of the response induced by the preconditioning stress or agents [e.g., H 2 O 2 (Tang et al, 2005), glutamate (Jiang et al, 2005), EPO (Baker, 2005), duration of ischemia (Cokkinos, 2002;Kloner, 1997), and FCCP (a potential mitochondrial uncoupler) (Brennan et al, 2006)].…”

Section: Ischemic Preconditioningsupporting

confidence: 80%

Pharmacological Enhancement of Neuronal Survival

Calabrese

2008

Critical Reviews in Toxicology

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This article is a comprehensive assessment of the quantitative features of the dose response for neuroprotective agents and their underlying mechanistic foundations. The data were derived from published studies using numerous primary neuronal cell cultures and neuronal cell lines. These biological models assessed normal developmental and aging processes, preconditioning adaptive responses, and various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. The nature of the dose response was generally U-shaped with quantitative features similar to the hormetic dose-response model and independent of biological model, endpoint measured, and chemical class. The agents displaying the U-shaped dose response for neuronal survival include numerous endogenous agonists, plant-derived agents, synthetic drugs, and widely used chemicals including potent neurotoxins. That neuroprotective agents display similar dose-response relationships regardless of experimental system, potency, and endpoint is an important observation with widespread biomedical and clinical implications.

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“…Transgenic and knockout mouse models have contributed to our understanding of the protective role of the heat shock response in mammals. Hsf1 knockouts are often more sensitive to stressors (Yan et al 2002;Wirth et al 2003;Christians and Benjamin 2005). Indeed, Hsf1 knockouts have provided genetic evidence for the protective role of the heat shock response in the cochlea.…”

Section: Discussionmentioning

confidence: 99%

Induction of Heat Shock Proteins by Hyperthermia and Noise Overstimulation in Hsf1 −/− Mice

Gong

Fairfield

Fullarton

et al. 2011

JARO

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Diverse cellular and environmental stresses can activate the heat shock response, an evolutionarily conserved mechanism to protect proteins from denaturation. Stressors activate heat shock transcription factor 1 (HSF1), which binds to heat shock elements in the genes for heat shock proteins, leading to rapid induction of these important molecular chaperones. Both heat and noise stress are known to activate the heat shock response in the cochlea and protect it from subsequent noise trauma. However, the contribution of HSF1 to induction of heat shock proteins following noise trauma has not been investigated at the molecular level. We evaluated the role of HSF1 in the cochlea following noise stress by examining induction of heat shock proteins in Hsf1 +/− control and Hsf1 −/− mice. Heat stress rapidly induced expression of Hsp25, Hsp47, Hsp70.1, Hsp70.3, Hsp84, Hsp86, and Hsp110 in the cochleae of wild-type and Hsf1 +/− mice, but not in Hsf1 −/− mice, confirming the essential role of HSF1 in mediating the heat shock response. Exposure to broadband noise (2-20 kHz) at 106 dB SPL for 2 h produced partial hearing loss. Maximal induction of heat shock proteins occurred 4 h after the noise. In comparison to heat stress, noise stress resulted in lower induced levels of Hsp25, Hsp70.1, Hsp70.3, Hsp86, and Hsp110 in Hsf1 +/− mice. Induction of these heat shock proteins was attenuated, but not completely eliminated, in Hsf1 −/− mice. These same noise exposure conditions induced genes for several immediate early transcription factors and maximum induction occurred earlier than for heat shock proteins. Thus, additional signaling pathways and transcriptional regulators that are activated by noise probably contribute to induction of heat shock proteins in the cochlea.

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Use of Hsf1−/− mice reveals an essential role for HSF1 to protect lung against cadmium-induced injury

Cited by 26 publications

References 37 publications

Cadmium-mediated activation of the HSP90/HSF1 pathway regulated by reactive persulfides/polysulfides

Cadmium-mediated activation of the HSP90/HSF1 pathway regulated by reactive persulfides/polysulfides

Pharmacological Enhancement of Neuronal Survival

Induction of Heat Shock Proteins by Hyperthermia and Noise Overstimulation in Hsf1 −/− Mice

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