Prolonged Protein Turnover of Glyceraldehyde-3-Phosphate Dehydrogenase by Phospholipase C-gamma 1 is Critical for Anchorage-Independent Growth and ATP Synthesis in Transformed Cells

Yun, Jae Won; Kim, Sungkuk; Kim, Ho

doi:10.3109/07357907.2010.535062

Cited by 4 publications

(2 citation statements)

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“…The increase in GAPDH may be a direct result of inhibition of the proteasome because intracellular amounts of GAPDH are regulated by ubiquitination [31], [32]. Another mechanism may be involved in regulation of CAND1 by MG132.…”

Section: Discussionmentioning

confidence: 99%

Treatment with the Proteasome Inhibitor MG132 during the End of Oocyte Maturation Improves Oocyte Competence for Development after Fertilization in Cattle

et al. 2012

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Maturation of the oocyte involves nuclear and cytoplasmic changes that include post-translational processing of proteins. The objective was to investigate whether inhibition of proteasomes during maturation would alter competence of the bovine oocyte for fertilization and subsequent development. Cumulus-oocyte complexes were cultured in the presence or absence of the proteasomal inhibitor MG132 from either 0–6 h or 16–22 h after initiation of maturation. Treatment with MG132 early in maturation prevented progression to meiosis II and reduced fertilization rate and the proportion of oocytes and cleaved embryos that became blastocysts. Conversely, treatment with MG132 late in maturation improved the percentage of oocytes and cleaved embryos that became blastocysts without affecting nuclear maturation or fertilization rate. Optimal results with MG132 were achieved at a concentration of 10 µM – effects were generally not observed at lower or higher concentrations. Using proteomic analysis, it was found that MG132 at the end of maturation increased relative expression of 6 proteins and decreased relative expression of 23. Among those increased by MG132 that are potentially important for oocyte competence are GAPDH, involved in glycolysis, TUBA1C, needed for organellar movement, and two proteins involved in protein folding (P4HB and HYOU1). MG132 decreased amounts of several proteins that exert anti-apoptotic actions including ASNS, HSP90B1, PDIA3 and VCP. Another protein decreased by MG132, CDK5, can lead to apoptosis if aberrantly activated and one protein increased by MG132, P4HB, is anti-apoptotic. Finally, the pregnancy rate of cows receiving embryos produced from oocytes treated with MG132 from 16–22 h of maturation was similar to that for control embryos, suggesting that use of MG132 for production of embryos in vitro does not cause a substantial decrease in embryo quality.

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Section: Discussionmentioning

confidence: 99%

Treatment with the Proteasome Inhibitor MG132 during the End of Oocyte Maturation Improves Oocyte Competence for Development after Fertilization in Cattle

et al. 2012

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“…After incubating cells for 4 weeks, foci in the 0.35% agarose layer were identified and photographed [36].…”

Section: Brdu Uptakementioning

confidence: 99%

Cells Transformed by PLC-Gamma 1 Overexpression are Highly Sensitive to Clostridium difficile Toxin A-Induced Apoptosis and Mitotic Inhibition

Nam

Kang²,

Chang³

et al. 2012

J. Microbiol. Biotechnol.

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Phospholipase C-γl (PLC-γl) expression is associated with cellular transformation. Notably, PLC-γ is up-regulated in colorectal cancer tissue and breast carcinoma. Because exotoxins released by Clostridium botulinum have been shown to induce apoptosis and promote growth arrest in various cancer cell lines, we examined here the potential of Clostridium difficile toxin A to selectively induce apoptosis in cells transformed by PLC-γl overexpression. We found that PLC-γl-transformed cells, but not vectortransformed (control) cells, were highly sensitive to C. difficile toxin A-induced apoptosis and mitotic inhibition. Moreover, expression of the proapoptotic Bcl2 family member, Bim, and activation of caspase-3 were significantly up-regulated by toxin A in PLC-γl-transformed cells. Toxin A-induced cell rounding and paxillin dephosphorylation were also significantly higher in PLC-γl-transformed cells than in control cells. These findings suggest that C. difficile toxin A may have potential as an anticancer agent against colorectal cancers and breast carcinomas in which PLC-γl is highly up-regulated.

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Impact of hexavalent chromium on mammalian cell bioenergetics: phenotypic changes, molecular basis and potential relevance to chromate-induced lung cancer

et al. 2014

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Occupational exposure to hexavalent chromium [Cr(VI)] has been firmly associated with the development of several pathologies, notably lung cancer. According to the current paradigm, the evolution of normal cells to a neoplastic state is accompanied by extensive metabolic reprogramming, namely at the level of energy-transducing processes. Thus, a complete understanding of the molecular basis of Cr(VI)-induced lung cancer must encompass the elucidation of the impact of Cr(VI) on metabolism. Research in this area is still in its infancy. Nonetheless, Cr(VI)-induced metabolic phenotypes are beginning to emerge. Specifically, it is now well documented that Cr(VI) exposure inhibits respiration and negatively affects the cellular energy status. Furthermore, preliminary results suggest that it also upregulates glucose uptake and lactic acid fermentation. From a mechanistic point of view, there is evidence that Cr(VI) exposure can interfere with energy transducing pathways at different levels, namely gene expression, intracellular protein levels and/or protein function. Loss of thiol redox control likely plays a key role in these processes. The transcriptional networks that control energy transduction can likewise be affected. Data also suggest that Cr(VI) exposure might compromise energy transducing processes through changes in the intracellular pools of their substrates. This article reviews, for the first time, the information available on Cr(VI) impact on mammalian cell bioenergetics. It aims to provide a framework for the understanding of the role played by bioenergetics in Cr(VI)-induced carcinogenesis and is also intended as a guide for future research efforts in this area.

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Prolonged Protein Turnover of Glyceraldehyde-3-Phosphate Dehydrogenase by Phospholipase C-gamma 1 is Critical for Anchorage-Independent Growth and ATP Synthesis in Transformed Cells

Cited by 4 publications

References 39 publications

Treatment with the Proteasome Inhibitor MG132 during the End of Oocyte Maturation Improves Oocyte Competence for Development after Fertilization in Cattle

Treatment with the Proteasome Inhibitor MG132 during the End of Oocyte Maturation Improves Oocyte Competence for Development after Fertilization in Cattle

Cells Transformed by PLC-Gamma 1 Overexpression are Highly Sensitive to Clostridium difficile Toxin A-Induced Apoptosis and Mitotic Inhibition

Impact of hexavalent chromium on mammalian cell bioenergetics: phenotypic changes, molecular basis and potential relevance to chromate-induced lung cancer

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