Functional analysis of clusterin/apolipoprotein J in cellular death induced by severe genotoxic stress

Annals of the New York Academy of Sciences
Ioannis Trougakos, Efstathios S Gonos

Abstract

Clusterin/apolipoprotein J (CLU) is a secreted heterodimeric glycoprotein that is reportedly upregulated during tumorigenesis, as well as during cell injury or death. Despite extensive efforts, CLU function during cellular death remains largely elusive. We are using as a model system to study CLU function three human osteosarcoma (OS) cell lines, namely, Sa OS, KH OS, and U-2 OS cells, induced to die after exposure to severe genotoxic stress mediated by the chemotherapeutic drug doxorubicin (DXR). We initially applied small interfering RNA (siRNA)-mediated specific knockdown of the CLU protein in OS cells. In all three cell lines, CLU knockdown resulted in increased sensitization to DXR-induced apoptosis. Supportively, moderate levels of forced transgene-mediated CLU stable overexpression in KH OS cells could rescue them from DXR-mediated apoptosis. In contrast, stable overexpression of high CLU levels in Sa OS and U-2 OS cells augmented apoptosis induced by cell exposure to severe DXR-mediated genotoxic stress. In summary, our data provide evidence that, although CLU is essential for cellular homeostasis, it may become highly cytotoxic in certain cellular contexts when it accumulates in high amounts intracellularly either by d...Continue Reading

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Aug 30, 2002·The International Journal of Biochemistry & Cell Biology·Ioannis P Trougakos, Efstathios S Gonos
Jun 12, 2003·Journal of Cell Science·Laure DebureDenis Michel

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Citations

Apr 8, 2011·Age·Mónica Santos-GonzálezJosé M Villalba
May 11, 2012·The International Journal of Biochemistry & Cell Biology·Amina Zoubeidi, Martin Gleave
Mar 17, 2009·Journal of Cellular Physiology·Tehila Kaisman-ElbazWilliam F Silverman
Jan 9, 2013·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Sandra GottschlingMichael Meister
Dec 17, 2016·Expert Opinion on Therapeutic Targets·Mark R Wilson, Amina Zoubeidi
Dec 17, 2009·American Journal of Physiology. Renal Physiology·Wenjun ZhouCaigan Du

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