Inhibition of cytosolic and mitochondrial creatine kinase by siRNA in HaCaT- and HeLaS3-cells affects cell viability and mitochondrial morphology.

Inhibition of cytosolic and mitochondrial creatine kinase by siRNA in HaCaT- and HeLaS3-cells affects cell viability and mitochondrial morphology. Research Abstract Details 

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Inhibition of cytosolic and mitochondrial creatine kinase by siRNA in HaCaT- and HeLaS3-cells affects cell viability and mitochondrial morphology. Abstract Text:

Holger Lenz,Melanie Schmidt,Vivienne Welge,Thomas Kueper,Uwe Schlattner,Theo Wallimann,Hans-Peter ,Klaus-Peter Wittern,Horst Wenck,Franz Staeb,Thomas Blatt,Holger Lenz,Melanie Schmidt,Vivienne Welge,Thomas Kueper,Uwe Schlattner,Theo Wallimann,Hans-Peter ,Klaus-Peter Wittern,Horst Wenck,Franz Staeb,Thomas Blatt,

The creatine kinase (CK) system is essential for cellular energetics in tissues or cells with high and fluctuating energy requirements. Creatine itself is known to protect cells from stress-induced injury. By using an siRNA approach to silence the CK isoenzymes in human keratinocyte HaCaT cells, expressing low levels of cytoplasmic CK and high levels of mitochondrial CK, as well as HeLa cancer cells, expressing high levels of cytoplasmic CK and low levels of mitochondrial CK, we successfully lowered the respective CK expression levels and studied the effects of either abolishing cytosolic brain-type BB-CK or ubiquitous mitochondrial uMi-CK in these cells. In both cell lines, targeting the dominant CK isoform by the respective siRNAs had the strongest effect on overall CK activity. However, irrespective of the expression level in both cell lines, inhibition of the mitochondrial CK isoform generally caused the strongest decline in cell viability and cell proliferation. These findings are congruent with electron microscopic data showing substantial alteration of mitochondrial morphology as well as mitochondrial membrane topology after targeting uMi-CK in both cell lines. Only for the rate of apoptosis, it was the least expressed CK present in each of the cell lines whose inhibition led to the highest proportion of apoptotic cells, i.e., downregulation of uMi-CK in case of HeLaS3 and BB-CK in case of HaCaT cells. We conclude from these data that a major phenotype is linked to reduction of mitochondrial CK alone or in combination with cytosolic CK, and that this effect is independent of the relative expression levels of Mi-CK in the cell type considered. The mitochondrial CK isoform appears to play the most crucial role in maintaining cell viability by stabilizing contact sites between inner and outer mitochondrial membranes and maintaining local metabolite channeling, thus avoiding transition pore opening which eventually results in activation of caspase cell-death pathways.

Inhibition of cytosolic and mitochondrial creatine kinase by siRNA in HaCaT- and HeLaS3-cells affects cell viability and mitochondrial morphology. Publishing Authors By Initials

H Lenz,M Schmidt,V Welge,T Kueper,U Schlattner,T Wallimann,HP ,KP Wittern,H Wenck,F Staeb,T Blatt,H Lenz,M Schmidt,V Welge,T Kueper,U Schlattner,T Wallimann,HP ,KP Wittern,H Wenck,F Staeb,T Blatt,

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Inhibition of cytosolic and mitochondrial creatine kinase by siRNA in HaCaT- and HeLaS3-cells affects cell viability and mitochondrial morphology. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular and cellular biochemistry

VOLUME: 306

Page Numbers: 153-62

Journal Abbreviation: Mol. Cell. Biochem.

ISSN: 0300-8177

DAY: 28

MONTH: 07

YEAR: 2007

Inhibition of cytosolic and mitochondrial creatine kinase by siRNA in HaCaT- and HeLaS3-cells affects cell viability and mitochondrial morphology. Information

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LANGUAGE: eng

NlmUniqueID: 364456

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Grant and Affiliation Information for Inhibition of cytosolic and mitochondrial creatine kinase by siRNA in HaCaT- and HeLaS3-cells affects cell viability and mitochondrial morphology.

AFFILIATION: R&D, Beiersdorf AG, Unnastrasse 48, 20245 Hamburg, Germany. holger.lenz@beiersdorf.com

Country: Netherlands

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MEDLINETA: Mol Cell Biochem

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