Relationship between cadmium-induced expression of heatshock genes, inhibition of protein synthesis and cell death

Ovelgönne, J. H.; Souren, J. E. M.; Wiegant, F. A. C.; Wijk, R. van

doi:10.1016/0300-483x(94)02990-c

Cited by 60 publications

(22 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Particularly, in avoiding competition in the cell through a host shutoff mechanism does the virus trigger incidentally the induction of heat responsive genes, albeit to advantage? This could occur through a block to host protein synthesis since induced HSP expression has been observed when protein synthesis is inhibited (27). The abrupt induction of HSP at the infection front gives no indication of a time delay between it and mRNA depletion.…”

Section: Discussionmentioning

confidence: 99%

Induction of HSP70 and polyubiquitin expression associated with plant virus replication

Aranda

Escaler

Wang

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

136

107

View full text Add to dashboard Cite

By examining the front of virus invasion in immature pea embryos infected with pea seed-borne mosaic virus (PSbMV), the selective control of different host genes has been observed. From our observations, the early responses to PSbMV replication can be grouped into three classes, inhibited host gene expression, induced host gene expression, and no effect on a normal host function. The expression of two heat-inducible genes encoding HSP70 and polyubiquitin was induced coordinately with the onset of virus replication and the down-regulation of two other genes encoding lipoxygenase and heat shock cognate protein. The down-regulation was part of a general suppression of host gene expression that may be achieved through the degradation of host transcripts. We discuss the possibilities of whether the induction of HSP70 and polyubiquitin genes represents a requirement for the respective protein products by the virus or is merely a consequence of the depletion of other host transcripts. The former is feasible, as the induction of both genes does result in increased HSP70 and ubiquitin accumulation. This also indicates that, in contrast to some animal virus infections, there is not a general inhibition of translation of host mRNAs following PSbMV infection. This selective control of host gene expression was observed in all cell types of the embryo and identifies mechanisms of cellular disruption that could act as triggers for symptom expression.For maximum efficiency, a virus must balance the exploitation of host cellular processes against consequential cellular damage. How this is achieved is not well understood. However, examples from a wide range of animal viruses (reviewed in ref. 1) and our earlier work with the plant virus pea seed-borne mosaic virus (PSbMV; ref.2) suggest that a major component in the control exerted by the virus is the shutoff of transcription and͞or translation of host mRNAs. Because the virus must use the host machinery for polynucleotide and protein synthesis, either the control must be highly selective or virus replication must depend on long-lived host mRNAs and͞or proteins. A similar argument may also apply to the use of host processes for the correct folding and turnover of viral proteins.The host shutoff phenomenon has been studied in most detail for poliovirus in which viral proteins interfere with DNA polymerase I, II, and III transcription (3-5) and translation (6, 7) and for herpes simplex virus 1 in which host translation is inhibited and there is a rapid degradation of capped mRNAs by a viral protein with riboexonuclease activity (8). For PSbMV replicating in pea embryonic tissues, there is a transient host shutoff associated with a loss of host gene transcripts associated with diverse areas of metabolism (2).In common with all viruses, PSbMV replication is associated with the translation of viral RNA and the multifarious activities of virus-encoded proteins. Hence, the basic translational machinery and processes required to assist in the correct folding and turnover of prote...

show abstract

Section: Discussionmentioning

confidence: 99%

Induction of HSP70 and polyubiquitin expression associated with plant virus replication

Aranda

Escaler

Wang

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

136

107

View full text Add to dashboard Cite

show abstract

“…Stimulation of this promoter is in line with HSP induction by many other toxicants including alkylating agents, toxic metals, and quinone methides [50]. It has been suggested that increase in HSP expression may be a direct result of alterations in protein structure through adduct formation; a secondary consequence of decreased non-protein thiol groups and formation of disulfide linkages between proteins [51]; or of release of metal ions due to alkylation of metal-sequesting proteins [52]. The 78-kDa glucose regulated protein (GRP78) is a major endoplasmic reticulum (ER) protein that functions as a chaperone.…”

Section: Gene Profile Assaymentioning

confidence: 96%

Differential Cytotoxicity and Gene Expression in Human Liver Carcinoma (HepG2) Cells Exposed to Arsenic Trioxide, and Monosodium Acid Methanearsonate (MSMA)

Tchounwou

Wilson

Abdelghani

et al. 2002

IJMS

View full text Add to dashboard Cite

Abstract:Research in our laboratory has demonstrated that a trivalent form of arsenic such as arsenic trioxide (AT) has the ability to cause significant cytotoxicity, and induction of a significant number of stress genes in human liver carcinoma cells (HepG 2 ). However, the literature also indicates that the toxicity of arsenic depends on its chemical form. To test this hypothesis, we further evaluated the cellular and molecular responses of HepG 2 cells following exposure to monosodium acid methanearsonate (MSMA), a pentavalent and organic form of arsenic. Cytotoxicity was evaluated using the MTT-assay for cell viability, while the gene profile assay was performed to measure the degree of gene induction in 13 different recombinant cell lines generated from a parental HepG 2 cell line. Cytotoxicity experiments yielded LC 50 values of 11.9 + 2.6 µg/mL for AT, and 257.3 + 51.4µg/mL for MSMA; indicating that AT was about 20 times more toxic than MSMA. Exposure of HepG 2 cells to MSMA also resulted in a significant reduction (p < 0.05) in the number of stress genes induced, compared to AT. Upon MSMA exposure, only 2 (HMTIIA and HSP70) out of the 13 constructs evaluated yielded inductions to statistically significant levels (p < 0.05), compared to 11 (GSTYa, XRE, HMTIIA, c-fos, NF-kBRE, HSP70, p53RE, GADD153, GADD45, and GRP78) for AT. These results greatly support the hypothesis that the toxicity of arsenic compounds highly depends on their chemical forms; with the inorganic forms being more potent than the organic ones.

show abstract

“…To elucidate the mechanism responsible for the lack of Hsp induction, we examined several stages of the hsp gene expression pathway, including transcription factor activity, Hsp70 mRNA production and protein synthesis chaperoning. Interestingly, the exposure of isolated hepatocytes to cadmium chloride, a chemical inducer of the HSR (Lai et al, 1993;Ovelgonne et al, 1995;Liao and Freedman, 1998), also failed to stimulate the production of Hsps . This result suggests that an anomaly exists in the expression of hsp genes in this species, rather than insensitivity to temperature per se.…”

mentioning

confidence: 99%

Regulation of heat shock genes in isolated hepatocytes from an Antarctic fish,Trematomus bernacchii

Buckley

Place

Hofmann

2004

Journal of Experimental Biology

123

View full text Add to dashboard Cite

patterns, in hepatocytes from T. bernacchii. Hsp70 mRNA was detected, as was heat shock factor 1 (HSF1) with DNA-binding activity. However, exposure to elevated temperature and to chemical inducers of the heat shock response failed to increase Hsp70 mRNA levels, HSF1 activity or the concentration of any size class of Hsps. These results suggest that Hsps, inducible in nearly every other species, are expressed constitutively in the coldadapted T. bernacchii.

show abstract

Relationship between cadmium-induced expression of heatshock genes, inhibition of protein synthesis and cell death

Cited by 60 publications

References 48 publications

Induction of HSP70 and polyubiquitin expression associated with plant virus replication

Induction of HSP70 and polyubiquitin expression associated with plant virus replication

Differential Cytotoxicity and Gene Expression in Human Liver Carcinoma (HepG2) Cells Exposed to Arsenic Trioxide, and Monosodium Acid Methanearsonate (MSMA)

Regulation of heat shock genes in isolated hepatocytes from an Antarctic fish,Trematomus bernacchii

Contact Info

Product

Resources

About