Autophagy in normal and malignant liver cells
1. Research group name/project:
Autophagy in normal and malignant liver cells
2. Group leader and some key members (incl. from other depts./inst.):
Per O. Seglen, prof. (group leader); Monica Fengsrud, Ph.D. (autophagy); Hamid R. Samari, M.Sc. (phosphosignalling; IT); Anders Øverbye, M.Sc. (proteomics)
3. Home address on the internet:
http://radium.no/seglen
4. Department/Institute:
Proteomics & Mammalian Cell Biology Section, Department of Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital
5. Main aim of research group:
Autophagy is a process by which cells, under conditions of stress or starvation, digest their own cytoplasm to obtain small molecules (like amino acids) needed for maintenance and renewal of essential cell functions. The aim of the project is to elucidate the molecular basis of autophagy, and to characterize the signalling pathways that regulate autophagy in normal cells (but not in cancer cells).
6. Some important recent results (with a few key references):
The project has developed a method for purification of autophagic organelles (autophagosomes) from isolated rat liver cells (Strømhaug et al. 1998, Biochem. J. 335, 217-224), and used proteomic methods (protein separation by two-dimensional gel electrophoresis and column chromatography, combined with protein identification by mass spectrometry) to identify about 40 proteins selectively associated with autophagosomal membranes, including many novel enzyme forms (Fengsrud et al. 2000, Biochem. J. 352, 773-781). The project has, furthermore, identified a signalling pathway that shuts down autophagy during toxic stress. This pathway, which includes the AMP-activated protein kinase (AMPK), the stress-activated kinases SEK1 and JNK, and possibly S6-kinase (Ruud Larsen et al. 2002, J.Biol.Chem. 277, 34826-34835), also appears to regulate cytoskeletal organization and apoptotic cell death. A grapefuit flavonoid, naringin, inhibits AMPK phosphorylation, autophagy suppression and toxin-induced death of normal cells, but not of cancer cells (Blankson et al. 2000, Cell Death Differ. 7, 739-746).
7. Methods in current use:
Proteomics (2D- and RP-LC protein fractionation; protein identification by MALDI-TOF tryptic peptide mass fingerprinting); isolation and culture of rat liver cells; subcellular fractionation (e.g., isolation of autophagosomes), 1D- and 2D-immunoblotting; measurement of autophagic activity
8. Available equipment:
MALDI-TOF mass spectrometer (Voyager DePro, Applied Biosystems)
9. Collaborators:
9.1. Among Helse Sør hospitals : Other research groups at the Norwegian Radium Hospital
9.2. Other Norwegian collaborators: Trond Berg, Dept. of Molecular Bioscience, UiO; Leon Reubsaet, Dept. of Pharmacy, UiO; Kristian F. Hanssen, Diabetes Research Centre, Aker sykehus
9.3. Collaborators from other countries:
10. Some key search words:
AMPK, apoptosis, autophagy, cytoskeleton, flavonoid, hepatocyte, liver, mass spectrometry, naringin, okadaic acid, plectin, proteomics, rat, toxin
Autophagy in normal and malignant liver cells
2. Group leader and some key members (incl. from other depts./inst.):
Per O. Seglen, prof. (group leader); Monica Fengsrud, Ph.D. (autophagy); Hamid R. Samari, M.Sc. (phosphosignalling; IT); Anders Øverbye, M.Sc. (proteomics)
3. Home address on the internet:
http://radium.no/seglen
4. Department/Institute:
Proteomics & Mammalian Cell Biology Section, Department of Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital
5. Main aim of research group:
Autophagy is a process by which cells, under conditions of stress or starvation, digest their own cytoplasm to obtain small molecules (like amino acids) needed for maintenance and renewal of essential cell functions. The aim of the project is to elucidate the molecular basis of autophagy, and to characterize the signalling pathways that regulate autophagy in normal cells (but not in cancer cells).
6. Some important recent results (with a few key references):
The project has developed a method for purification of autophagic organelles (autophagosomes) from isolated rat liver cells (Strømhaug et al. 1998, Biochem. J. 335, 217-224), and used proteomic methods (protein separation by two-dimensional gel electrophoresis and column chromatography, combined with protein identification by mass spectrometry) to identify about 40 proteins selectively associated with autophagosomal membranes, including many novel enzyme forms (Fengsrud et al. 2000, Biochem. J. 352, 773-781). The project has, furthermore, identified a signalling pathway that shuts down autophagy during toxic stress. This pathway, which includes the AMP-activated protein kinase (AMPK), the stress-activated kinases SEK1 and JNK, and possibly S6-kinase (Ruud Larsen et al. 2002, J.Biol.Chem. 277, 34826-34835), also appears to regulate cytoskeletal organization and apoptotic cell death. A grapefuit flavonoid, naringin, inhibits AMPK phosphorylation, autophagy suppression and toxin-induced death of normal cells, but not of cancer cells (Blankson et al. 2000, Cell Death Differ. 7, 739-746).
7. Methods in current use:
Proteomics (2D- and RP-LC protein fractionation; protein identification by MALDI-TOF tryptic peptide mass fingerprinting); isolation and culture of rat liver cells; subcellular fractionation (e.g., isolation of autophagosomes), 1D- and 2D-immunoblotting; measurement of autophagic activity
8. Available equipment:
MALDI-TOF mass spectrometer (Voyager DePro, Applied Biosystems)
9. Collaborators:
9.1. Among Helse Sør hospitals : Other research groups at the Norwegian Radium Hospital
9.2. Other Norwegian collaborators: Trond Berg, Dept. of Molecular Bioscience, UiO; Leon Reubsaet, Dept. of Pharmacy, UiO; Kristian F. Hanssen, Diabetes Research Centre, Aker sykehus
9.3. Collaborators from other countries:
10. Some key search words:
AMPK, apoptosis, autophagy, cytoskeleton, flavonoid, hepatocyte, liver, mass spectrometry, naringin, okadaic acid, plectin, proteomics, rat, toxin
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