Overexpression of Mitochondrial Hsp70/Hsp75 Protects Astrocytes against Ischemic Injury <i>in vitro</i>

Voloboueva, Ludmila A.; Duan, Melissa; Ouyang, Yi‐Bing; Emery, John F.; Stoy, Christian; Giffard, Rona G.

doi:10.1038/sj.jcbfm.9600600

Cited by 109 publications

(101 citation statements)

References 45 publications

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“…We note that as for the H cybrid, the heat induction of HSP60 gene is in line with literature data, while the up-regulation of the HSP75 gene is unexpected, as it had been reported to be up-regulated by stresses different from heat (Hadari et al 1997;Ryan et al 1997;Carette et al 2002;Zhao et al 2002;Tokalov et al 2003;Murray et al 2004;Voloboueva et al 2008). Considering the role of the two HSPs in the processes of protein import into mitochondria and subsequent protein folding (Frydman 2001;Mokranjac and Neupert 2005;Saibil 2008), we could hypothesize that mtDNA variability modulates mRNA levels of HSP60 and HSP75 through transcription factors that coordinate the activity of the two genes.…”

Section: Discussionsupporting

confidence: 74%

Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines

Bellizzi

Taverna

D’Aquila

et al. 2009

Cell Stress and Chaperones

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To explore possible relationships between mitochondrial DNA (mtDNA) polymorphism and the expression levels of stress-responder nuclear genes we assembled five cybrid cell lines by repopulating 143B.TK − cells, depleted of their own mtDNA (Rho 0 cells), with foreign mitochondria with different mtDNA sequences (lines H, J, T, U, X). We evaluated, at both basal and under heat stress conditions, gene expression (mRNA) and intra-mitochondrial protein levels of HSP60 and HSP75, two key components in cellular stress response. At basal conditions, the levels of HSP60 and HSP75 mRNA were lower in one cybrid (H) than in the others (p=0.005 and p=0.001, respectively). Under stress conditions, the H line over-expressed both genes, so that the inter-cybrid difference was abolished. Moreover, the HSP60 intra-mitochondrial protein levels differed among the cybrid lines (p=0.001), with levels higher in H than in the other cybrid lines. On the whole, our results provide further experimental evidence that mtDNA variability influences the cell response to stressful conditions by modulating components involved in this response. Sentence summary of the article: the results reported in the present study provide important experimental evidence that in human cells mtDNA variability is able to influence the cellular response to heat stress by modulating both the transcription of genes involved in this response and their intra-mitochondrial protein levels.

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Section: Discussionsupporting

confidence: 74%

Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines

Bellizzi

Taverna

D’Aquila

et al. 2009

Cell Stress and Chaperones

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“…Genetic overexpression of the mitochondrial paralog of Hsp70 (mortalin/Grp75/mtHsp70) is sufficient to protect cultured primary astrocytes from ischemia-induced oxidative damage and death (Voloboueva et al, 2008). Likewise, mtHsp70 overexpression in brain reduced oxidative stress markers and improved mitochondrial function induced by ischemia/reperfusion (Xu et al, 2009).…”

Section: -Kda Heat-shock Protein and Neuroprotection In Dpnmentioning

confidence: 99%

Diabetic Peripheral Neuropathy: Should a Chaperone Accompany Our Therapeutic Approach?

Farmer

Dobrowsky

2012

Pharmacol Rev

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“…In addition to HSPA8 and YWHAE, heat shock protein 75 kDa (TRAP1) was predictive of treatment. Trap1 is another heat shock protein shown to protect against ischemic injury (Voloboueva et al 2008). The decrease in this protein may be associated with the observed extravasated erythrocytes resulting from damage to vessel walls (hemorrhage) and consequent formation of erythrophagosomes observed at 100 mg.…”

Section: Biomarkers Of Dysgenesis In Fetal Rat Testismentioning

confidence: 99%

Novel molecular targets associated with testicular dysgenesis induced by gestational exposure to diethylhexyl phthalate in the rat: a role for estradiol

Klinefelter¹,

Laskey²,

Winnik³

et al. 2012

Reproduction

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Significant research has been focused on phthalate-induced alterations in male reproductive development. Studies on rodents have prompted the notion that a syndrome exists in the human male which includes phenotypic alterations such as hypospadias, cryptorchidism, poor semen quality, and even testicular cancer. Each phenotype in this 'testicular dysgenesis syndrome' is predicated on reduction in testosterone production by the fetal Leydig cell. We sought to examine the relationship between dysgenesis and steroidogenic capacity in the fetal rat testis more stringently by incorporating lower exposures than those typically used, conducting a comprehensive, non-targeted quantitative evaluation of the fetal testis proteome, and relating alterations in individual proteins to the capacity of the fetal Leydig cell to produce testosterone, and histopathology of the fetal testis. Pregnant dams were dosed orally from gestation day (GD) 13-19 with 0, 10, or 100 mg diethylhexyl phthalate (DEHP)/kg body weight per day. Each endpoint was represented by 16 l. Clustering of Leydig cells occurred before any significant decrease in the capacity of the GD19 Leydig cell to produce testosterone. At 100 mg DEHP/kg, testosterone production was reduced significantly, Leydig cell clusters became quite large, and additional dysgenetic changes were observed in the fetal testis. Of 23 proteins whose expression was altered significantly at both DEHP exposure levels, seven were found to be correlated with and predictive of the quantified endpoints. None of these proteins have been previously implicated with DEHP exposure. Notably, pathway analysis revealed that these seven proteins fit a pathway network in which each is regulated directly or indirectly by estradiol.

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Overexpression of Mitochondrial Hsp70/Hsp75 Protects Astrocytes against Ischemic Injury in vitro

Cited by 109 publications

References 45 publications

Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines

Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines

Diabetic Peripheral Neuropathy: Should a Chaperone Accompany Our Therapeutic Approach?

Novel molecular targets associated with testicular dysgenesis induced by gestational exposure to diethylhexyl phthalate in the rat: a role for estradiol

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