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Difference between revisions of "Truksa 2015 Antioxid Redox Signal"

From Bioblast
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|abstract=To assess the effect of mitochondrially targeted vitamin E (VE) analogs on mitochondrial function and biogenesis.
|abstract=To assess the effect of mitochondrially targeted vitamin E (VE) analogs on mitochondrial function and biogenesis.


Mitochondrially targeted vitamin E succinate (MitoVES) is an efficient inducer of apoptosis in cancer cells. Here, we show that unlike its untargeted counterpart Ξ±-tocopheryl succinate, MitoVES suppresses proliferation of cancer cells at sub-apoptotic doses by way of affecting the mitochondrial DNA (mtDNA) transcripts. We found that MitoVES strongly suppresses the level of the displacement loop transcript followed by those of mtDNA genes coding for subunits of mitochondrial complexes. This process is coupled to the inhibition of mitochondrial respiration, dissipation of the mitochondrial membrane potential, and generation of reactive oxygen species. In addition, exposure of cancer cells to MitoVES led to decreased expression of TFAM and diminished mitochondrial biogenesis. The inhibition of mitochondrial transcription was replicated in vivo in a mouse model of HER2high breast cancer, where MitoVES lowered the level of mtDNA transcripts in cancer cells but not in normal tissue. Innovation: Our data show that mitochondrially targeted VE analogs represent a novel class of mitocans that not only induce apoptosis at higher concentrations but also block proliferation and suppress normal mitochondrial function and transcription at low, non-apoptogenic doses.
Mitochondrially targeted vitamin E succinate (MitoVES) is an efficient inducer of apoptosis in cancer cells. Here, we show that unlike its untargeted counterpart Ξ±-tocopheryl succinate, MitoVES suppresses proliferation of cancer cells at sub-apoptotic doses by way of affecting the mitochondrial DNA (mtDNA) transcripts. We found that MitoVES strongly suppresses the level of the displacement loop transcript followed by those of mtDNA genes coding for subunits of mitochondrial complexes. This process is coupled to the inhibition of mitochondrial respiration, dissipation of the mitochondrial membrane potential, and generation of reactive oxygen species. In addition, exposure of cancer cells to MitoVES led to decreased expression of TFAM and diminished mitochondrial biogenesis. The inhibition of mitochondrial transcription was replicated in vivo in a mouse model of HER2high breast cancer, where MitoVES lowered the level of mtDNA transcripts in cancer cells but not in normal tissue.
Β 
Our data show that mitochondrially targeted VE analogs represent a novel class of mitocans that not only induce apoptosis at higher concentrations but also block proliferation and suppress normal mitochondrial function and transcription at low, non-apoptogenic doses.


Our data indicate a novel, selective anti-cancer activity of compounds that act by targeting mitochondria of cancer cells, inducing significant alterations in mitochondrial function associated with transcription of mtDNA-coded genes. These changes subsequently result in the arrest of cell proliferation.
Our data indicate a novel, selective anti-cancer activity of compounds that act by targeting mitochondria of cancer cells, inducing significant alterations in mitochondrial function associated with transcription of mtDNA-coded genes. These changes subsequently result in the arrest of cell proliferation.
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}}
}}
{{Labeling
{{Labeling
|area=mt-Membrane, mtDNA;mt-genetics
|organism=Human, Mouse
|tissues=Lung;gill, Endothelial;epithelial;mesothelial cell, Blood cells, Genital
|model cell lines=Fibroblast, Other cell lines
|preparations=Intact cells
|diseases=Cancer
|topics=mt-Membrane potential
|couplingstates=ROUTINE
|substratestates=CII, ROX
|instruments=Oxygraph-2k
|instruments=Oxygraph-2k
|additional=Labels, [Epub ahead of print]
}}
}}

Revision as of 11:01, 3 March 2015

Publications in the MiPMap
Truksa J, Dong LF, Rohlena J, Stursa J, Vondrusova M, Goodwin J, Nguyen M, Kluckova K, Rychtarcikova Z, Lettlova S, Spacilova J, Stapelberg M, Zoratti M, Neuzil J (2015) Mitochondrially targeted vitamin E succinate modulates expression of mitochondrial DNA transcripts and mitochondrial biogenesis. Antioxid Redox Signal [Epub ahead of print].

Β» PMID:25578105

Truksa J, Dong LF, Rohlena J, Stursa J, Vondrusova M, Goodwin J, Nguyen M, Kluckova K, Rychtarcikova Z, Lettlova S, Spacilova J, Stapelberg M, Zoratti M, Neuzil J (2015) Antioxid Redox Signal

Abstract: To assess the effect of mitochondrially targeted vitamin E (VE) analogs on mitochondrial function and biogenesis.

Mitochondrially targeted vitamin E succinate (MitoVES) is an efficient inducer of apoptosis in cancer cells. Here, we show that unlike its untargeted counterpart Ξ±-tocopheryl succinate, MitoVES suppresses proliferation of cancer cells at sub-apoptotic doses by way of affecting the mitochondrial DNA (mtDNA) transcripts. We found that MitoVES strongly suppresses the level of the displacement loop transcript followed by those of mtDNA genes coding for subunits of mitochondrial complexes. This process is coupled to the inhibition of mitochondrial respiration, dissipation of the mitochondrial membrane potential, and generation of reactive oxygen species. In addition, exposure of cancer cells to MitoVES led to decreased expression of TFAM and diminished mitochondrial biogenesis. The inhibition of mitochondrial transcription was replicated in vivo in a mouse model of HER2high breast cancer, where MitoVES lowered the level of mtDNA transcripts in cancer cells but not in normal tissue.

Our data show that mitochondrially targeted VE analogs represent a novel class of mitocans that not only induce apoptosis at higher concentrations but also block proliferation and suppress normal mitochondrial function and transcription at low, non-apoptogenic doses.

Our data indicate a novel, selective anti-cancer activity of compounds that act by targeting mitochondria of cancer cells, inducing significant alterations in mitochondrial function associated with transcription of mtDNA-coded genes. These changes subsequently result in the arrest of cell proliferation. β€’ Keywords: Mitochondrial targeting, Vitamin E succinate, mtDNA, Complex II, Proliferation, Anticancer effect

β€’ O2k-Network Lab: CZ Prague Zeman J, CZ Prague Neuzil J, AU Queensland Neuzil J


Labels: MiParea: mt-Membrane, mtDNA;mt-genetics  Pathology: Cancer 

Organism: Human, Mouse  Tissue;cell: Lung;gill, Endothelial;epithelial;mesothelial cell, Blood cells, Genital  Preparation: Intact cells 

Regulation: mt-Membrane potential  Coupling state: ROUTINE 

HRR: Oxygraph-2k 

Labels, [Epub ahead of print]