Implication of PBP74/mortalin/GRP75 in the radio-adaptive response

Carette, Jan E.; Lehnert, Shirley; Chow, Terry Y.-K.

doi:10.1080/09553000110097208

Cited by 43 publications

(31 citation statements)

References 24 publications

(2 reference statements)

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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: 75%

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: 75%

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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“…Unlike some members of the HSP70 family, Hsp75 is not heat-inducible, but is upregulated by glucose deprivation (GD), oxidative injury, and ultraviolet A irradiation (Carette et al, 2002;Hadari et al, 1997;Lee, 2001). Studies have indicated that Hsp75 upregulation suppresses apoptosis induced by arsenite in lung epithelial cells (Lau et al, 2004), mercury in renal cells (Stacchiotti et al, 2006), and glucose starvation and ischemia reperfusion in lung cells (Gao et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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

Voloboueva

Duan

Ouyang

et al. 2007

J Cereb Blood Flow Metab

107

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Mitochondrial heat shock protein 70 (mtHsp70/Hsp75/Grp75/mortalin/TRAP-1/PBP74) is an essential mitochondrial chaperone and a member of the heat shock protein 70 (HSP70) family. Although many studies have shown the protective properties of overexpression of the cytosolic inducible member of the HSP70 family, Hsp72, few studies have investigated the protective potential of Hsp75 against ischemic injury. Mitochondria are one of the primary targets of ischemic injury in astrocytes. In this study, we analyzed the effects of Hsp75 overexpression on cellular levels of reactive oxygen species (ROS), mitochondrial membrane potential, ATP levels, and viability during the ischemia-like conditions of oxygen-glucose deprivation (OGD) or glucose deprivation (GD) in primary astrocytic cultures. We show that Hsp75 overexpression decreases ROS production and preserves mitochondrial membrane potential during GD, and preserves ATP levels and cell viability during OGD. These findings indicate that Hsp75 can provide protection against ischemia-like in vitro injury and suggest that it should be further studied as a potential candidate for protection against ischemic injury.

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“…Grp75 has been implicated in various biological processes of human cells (13) and has been shown to respond to numerous forms of stress, including ischemia (15), glucose deprivation (16), oxidative injury (22) and drug resistance (23). In addition, data from previous studies have shown that the treatment of IR led to the upregulation of the Grp75 protein (17,18). In this study, the expression of Grp75 induced by IR was highlighted and a dose/time-dependent induction of Grp75 expression in response to IR treatment was identified ( Fig.…”

Section: Discussionmentioning

confidence: 64%

“…Previous studies have reported that the expression of Grp75 is inducible in response to IR treatment (17,18). However, there is no evidence concerning whether the induction of the Grp75 gene depends on the amount of IR or the frequency of IR.…”

Section: The Expression Of Grp75 Was Induced By Ir In Pc12 Cellsmentioning

confidence: 64%

“…Previous studies have demonstrated that Grp75 levels appear to correlate with mitochondrial activity and biogenesis (14) and that Grp75 expression is induced by cerebral ischemia (15), glucose deprivation (16) and low doses of IR (17). The gene expression of Grp75 in HT29 and MCF-7 cells was upregulated following exposure to IR (17,18). To investigate the potential link between the expression of Grp75 and Topo IIα and how they affect cell proliferation in response to low dose IR, the IR-induced proliferation and Topo IIα expression levels in regular and Grp75-overexpressing PC12 cells were analyzed.…”

Section: Introductionmentioning

confidence: 99%

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Glucose-regulated protein 75 overexpression attenuates ionizing radiation-mediated injury in PC12 cells by inducing the expression of topoisomerase IIα

Guo

Yang

et al. 2012

Molecular Medicine Reports

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Abstract. Glucose-regulated protein 75 (Grp75), also known as mortalin/mthsp70/PBP74, is a member of the heat-shock protein 70 (HSP70) family. Grp75 is known to protect cells from stress-induced injury. Previous studies have shown that the expression of Grp75 is upregulated by a low dose of ionizing radiation (IR). To evaluate the protective role of Grp75 on cell proliferation in response to IR, Grp75 was overexpressed in a rat adrenal pheochromocytoma cell line (PC12). It was revealed that Grp75 overexpression desensitized PC12 cells to IR-mediated cell injury. In addition, the expression of topoisomerase IIα (Topo IIα) was downregulated in PC12 cells following γ-ray IR. The effect of Grp75 overexpression on Topo IIα expression was examined. It was revealed that Grp75 overexpression reversed the inhibitory effect of IR on Topo IIα expression. In conclusion, the data indicated that Grp75 overexpression attenuates IR-induced injury in PC12 cells by maintaining the expression of Topo IIα. IntroductionIonizing radiation (IR) induces a variety of cellular responses at clinically relevant doses. MCF-7 cells were arrested at the G1 and G2 phases of the cell cycle and MDA-MB231 cells were arrested at the G2 phase in response to IR (1,2). It has been demonstrated that X-rays at extremely low doses, between 1-5 cGy, stimulate cell proliferation, whereas at doses >1 Gy, IR is lethal to cells (3). Topoisomerase IIα (Topo IIα), a nuclear enzyme involved in a number of cellular processes, is necessary for eukaryotic survival. Topo IIα is significant in the replication and repair of DNA and takes part in chromosome condensation and segregation during mitosis (4). Previous studies have demonstrated that DNA Topo IIα expression levels correlate with chromatid radiosensitivity (5). Topo IIα has also been shown to play a significant role in male mouse meiosis and its activity is required at the metaphase-anaphase transition of the two meiotic divisions for proper chromosome disjunction (6,7). The expression of Topo IIα changes periodically during cell growth and therefore, Topo IIα is thought to be a marker of cell proliferation (8-10). Topo IIα expression is affected by numerous environmental factors, including heat-shock and IR. It has been reported that, if the activity of Topo IIα is restrained or the distribution of Topo IIα in cells changes as the result of genetic mutations, the aneuploid ratio of the cells increases (11,12).Grp75, a member of the HSP70 family, is involved in multiple functions that are required to maintain cell metabolism, including the stress response, cell proliferation and differentiation (13). Previous studies have demonstrated that Grp75 levels appear to correlate with mitochondrial activity and biogenesis (14) and that Grp75 expression is induced by cerebral ischemia (15), glucose deprivation (16) and low doses of IR (17). The gene expression of Grp75 in HT29 and MCF-7 cells was upregulated following exposure to IR (17,18). To investigate the potential link between the expression of Grp75 and Topo I...

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Implication of PBP74/mortalin/GRP75 in the radio-adaptive response

Abstract: The results support the view that while PBP74 is necessary to the adaptive response, it may not by itself be sufficient for the adaptive response to occur.

Cited by 43 publications

References 24 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

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

Glucose-regulated protein 75 overexpression attenuates ionizing radiation-mediated injury in PC12 cells by inducing the expression of topoisomerase IIα

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