| Autor: |
Cheimonidi C; Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, Athens 15784, Greece., Grivas IN; Inflammation Research Laboratory, Department of Immunology, Transgenic Technology Laboratory, Hellenic Pasteur Institute, Athens 11521, Greece., Sesti F; Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, Athens 15784, Greece., Kavrochorianou N; Inflammation Research Laboratory, Department of Immunology, Transgenic Technology Laboratory, Hellenic Pasteur Institute, Athens 11521, Greece., Gianniou DD; Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, Athens 15784, Greece., Taoufik E; Laboratory of Cellular and Molecular Neurobiology-Stem Cells, Hellenic Pasteur Institute, Athens 11521, Greece., Badounas F; Inflammation Research Laboratory, Department of Immunology, Transgenic Technology Laboratory, Hellenic Pasteur Institute, Athens 11521, Greece., Papassideri I; Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, Athens 15784, Greece., Rizzi F; Dipartimento di Medicina e Chirurgia, Universita di Parma, Parma 43125, Italy.; Istituto Nazionale Biostrutture e Biosistemi (I.N.B.B.), Roma 00136, Italy., Tsitsilonis OE; Department of Animal and Human Physiology, Faculty of Biology, National and Kapodistrian University of Athens, Athens 15784, Greece., Haralambous S; Inflammation Research Laboratory, Department of Immunology, Transgenic Technology Laboratory, Hellenic Pasteur Institute, Athens 11521, Greece., Trougakos IP; Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, Athens 15784, Greece. |
| Abstrakt: |
Clusterin (CLU) is an ATP-independent small heat shock protein-like chaperone, which functions both intra- and extra-cellularly. Consequently, it has been functionally involved in several physiological (including aging), as well as in pathological conditions and most age-related diseases, e.g., cancer, neurodegeneration, and metabolic syndrome. To address CLU function at an in vivo model we established CLU transgenic (Tg) mice bearing ubiquitous or pancreas-targeted CLU overexpression (OE). Our downstream analyses in established Tg lines showed that ubiquitous or pancreas-targeted CLU OE in mice affected antioxidant, proteostatic and metabolic pathways. Targeted OE of CLU in the pancreas, which also resulted in CLU upregulation in the liver likely via systemic effects, increased basal glucose levels in the circulation and exacerbated diabetic phenotypes. Furthermore, by establishing a syngeneic melanoma mouse tumor model we found that ubiquitous CLU OE suppressed melanoma cells growth, indicating a likely tumor suppressor function in early phases of tumorigenesis. Our observations provide in vivo evidence corroborating the notion that CLU is a potential modulator of metabolic and/or proteostatic pathways playing an important role in diabetes and tumorigenesis. |
