Kari Espolin Fladmarks bilde
Kari Espolin
Fladmark
Professor
Besøksadresse: 
HIB - Thormøhlensgt. 55
5020 Bergen
Postadresse: 
Postboks 7803
5020 Bergen
Telefon: 
+47 55 58 45 14
Last ned visittkort

Algegifter hjelper oss til å forstå hvordan våre egne celler virker

Hvert minutt begår 80 000 celler i kroppen din selvmord. Vi vet lite om hvordan disse celleselvmordene bestemmes og styres. Hvis det oppstår svikt i cellenes evne til å regulere celleselvmordene får dette fatale konsekvenser som f.eks. kreft, neurodegenrative sykdommer og AIDS.

Blågrønnalger kan produsere gifter som setter i gang celleselvmordet i alle type celler. Selv om algene nok produserer disse giftene for å beskytte seg mot å bli spist av laverestående dyr, er giftene allikevel de mest effektive igangsetterne av selvmord i humane cellekulturer som vi kjenner til.

Våre celler er hele tiden utsatt for ytre og indre signaler som forteller de enten at de skal dø,  fortsette å leve eller dele seg. Disse signalene må cellene hele tiden tolke opp mot hverandre, for så å ta en avgjørelse. Å dø kan ikke angres, cellens kontrollmekanismer for å dø er nok derfor langt mer avanserte enn de for fortsatt liv eller vekst. 

Å sette på og å ta av en fosfatgruppe på et protein, er cellenes vanligste måte å sende interne signaler på. Dette kalles proteinfosforylering og er en unik mekanisme for nettopp å sortere døds- og leve-signaler. Algetoksinene angriper nettopp fosforyleringsmekanismen i cellene.

I vårt arbeid bruker vi algegifter som verktøy for å forsøke og forstå hva som skjer under celleselvmord og for å studere hvilke tidlige mekanismer som er viktige for at cellen skal ta en avgjørelse om å dø.

Tidsskriftartikler
  • Kamil, Atif; Raae, Arnt Johan; Fjelldal, Per Gunnar; Koppang, Erling Olaf; Fladmark, Kari Espolin; Hordvik, Ivar. 2013. Comparative analysis of IgM sub-variants in salmonid fish and identification of a residue in mu 3 which is essential for MAb4C10 reactivity. Fish and Shellfish Immunology. 34: 667-672. doi: 10.1016/j.fsi.2012.12.006
  • Opsahl, Jill Anette; Ljostveit, Sonja; Saunders, Threrese Solstad; Risa, Kristin; Roepstorff, Peter; Fladmark, Kari Espolin. 2013. Identification of dynamic changes in proteins associated with the cellular cytoskeleton after exposure to okadaic acid. Marine Drugs. 11: 1763-1782. doi: 10.3390/md11061763
  • Hjørnevik, Linda Veka; Fismen, Lise; Young, Fiona M; Solstad, Terese; Fladmark, Kari Espolin. 2012. Nodularin exposure induces SOD1 phosphorylation and disrupts SOD1 co-localization with actin filaments. Toxins. 4: 1482-1499. doi: 10.3390/toxins4121482
  • Oveland, Eystein; Wergeland, Line; Hovland, Randi; Lorens, James; Gjertsen, Bjørn Tore; Fladmark, Kari Espolin. 2012. Ectopic expression of Flt3 kinase inhibits proliferation and promotes cell death in different human cancer cell lines. Cell Biology and Toxicology. 28: 201-212. doi: 10.1007/s10565-012-9216-z
  • de Vareilles, Mahut; Conceição, Luis E.C.; Gomez Requeni, Pedro; Kousoulaki, Katerina; Richard, Nadège; Rodrigues, Pedro M.; Fladmark, Kari Espolin; Rønnestad, Ivar. 2012. Dietary lysine imbalance affects muscle proteome in zebrafish (Danio rerio): a comparative 2D-DIGE study. Marine Biotechnology. 14: 643-654. doi: 10.1007/s10126-012-9462-3
  • de Vareilles, Mahut; Richard, Nadège; Gavaia, Paulo J.; Silva, Tomé S.; Cordeiro, Odete; Guerreiro, Inês; Yúfera, Manuel; Batista, Irineu; Pires, Carla; Pousao-Ferreira, Pedro; Rodrigues, Pedro M.; Rønnestad, Ivar; Fladmark, Kari Espolin; Conceição, Luís E.C. 2012. Impact of dietary protein hydrolysates on skeleton quality and proteome in Diplodus sargus larvae. Journal of Applied Ichthyology. 28: 477-487. doi: 10.1111/j.1439-0426.2012.01986.x
  • Opsahl, Jill Anette; Hjørnevik, Linda Veka; Bull, Vibeke Hervik; Fismen, Lise; Frøyset, Ann Kristin; Gromyko, Darina; Solstad, Therese; Fladmark, Kari Espolin. 2010. Increased interaction between DJ-1 and the Mi-2/nucleosome remodelling and deacetylase complex during cellular stress. Proteomics. 10: 1494-1504. doi: 10.1002/pmic.200900586
  • Herfindal, Lars; Kasprzykowski, Franciszek; Schwede, Frank; Lankiewicz, Leszek; Fladmark, Kari Espolin; Lukomska, Joanna; Wahlsten, Matti; Sivonen, Kaarina; Grzonka, Zbigniew; Jastorff, Bernd; Doskeland, Stein Ove. 2009. Acyloxymethyl esterification of Nodularin-R and Microcystin-LA produces inactive protoxins that become reactivated and produce apoptosis inside intact cells. Journal of Medicinal Chemistry. 52: 5758-5762. doi: 10.1021/jm900502e
  • Kellmann, Ralf; Schaffner, Carlos António Markus; Grønset, Toril Anne; Satake, Masayuki; Ziegler, Mathias; Fladmark, Kari Espolin. 2009. Proteomic response of human neuroblastoma cells to azaspiracid-1. Journal of Proteomics. 72: 695-707. doi: 10.1016/j.jprot.2009.02.008
  • Oveland, Eystein; Gjertsen, Bjørn Tore; Wergeland, Line; Selheim, Frode; Fladmark, Kari Espolin; Hovland, Randi. 2009. Ligand-induced Flt3-downregulation modulates cell death associated proteins and enhances chemosensitivity to idarubicin in THP-1 acute myeloid leukemia cells. Leukemia research : a Forum for Studies on Leukemia and Normal Hemopoiesis. 33: 276-287. doi: 10.1016/j.leukres.2008.06.029
  • Solstad, Therese; Bull, Vibeke Hervik; Breivik, Lars Ertesvåg; Fladmark, Kari Espolin. 2008. Identification of protein interaction partners by immunoprecipitation: Possible pitfalls and false positives. Experimental and Clinical Hepatology. 4: 16-22.
  • Solstad, Therese; Fismen, Lise; Garberg, Hilde Kristin; Fladmark, Kari Espolin. 2008. Identification of a novel phosphorylation site of acyl-CoA binding protein (ACBP) in nodularin-induced apoptotic hepatocytes. Experimental Cell Research. 314: 2141-2149. doi: 10.1016/j.yexcr.2008.03.014
  • Målen, Hiwa; Berven, Frode; Fladmark, Kari Espolin; Wiker, Harald G. 2007. Comprehensive analysis of exported proteins from Mycobacterium tuberculosis H37Rv. Proteomics. 7: 1702-1718. doi: 10.1002/pmic.200600853
  • Brøgger, Jan Christian; Fladmark, Kari Espolin. 2006. Proteomic tissue imaging for rapid brain biomarker discovery. European Journal of Neurology. 13: 42-42.
  • Krakstad, Camilla; Herfindal, Lars; Gjertsen, Bjørn Tore; Bøe, Roald; Vintermyr, Olav Karsten; Fladmark, Kari Espolin; Doskeland, Stein Ove. 2006. CaM-kinasell-dependent commitment to microcystin-induced apoptosis is coupled to cell budding, but not to shrinkage or chromatin hypercondensation. Cell Death and Differentiation. 13: 1191-1202. doi: 10.1038/sj.cdd.4401798
  • Oveland, Eystein; Fladmark, Kari Espolin; Wergeland, Line; Gjertsen, Bjørn Tore; Hovland, Randi. 2006. Proteomics approaches to elucidate oncogenic tyrosine kinase signaling in myeloid malignancies. Current Pharmaceutical Biotechnology. 7: 185-198. doi: 10.2174/138920106777549696
  • Solstad, Therese; Fladmark, Kari Espolin. 2006. Algal toxins as guidance to identify phosphoproteins with key roles in apoptotic cell death. Current Pharmaceutical Biotechnology. 7: 209-215. doi: 10.2174/138920106777549704
  • Gausdal, Gro; Gjertsen, Bjørn Tore; Fladmark, Kari Espolin; Demol, H.; Vandekerckhove, Joel; Døskeland, Stein Ove. 2004. Caspase-dependent, geldanamycin-enhanced cleavage of co-chaperone p23 in leukemic apoptosis. Leukemia. 18: 1989-1996.
  • Fladmark, Kari Espolin. 2003. PROBE-nasjonal plattform i proteomikk. NBS-nytt. 2: 23-24.
  • Grav, Hans J; Tronstad, Karl J.; Gudbrandsen, Oddrun A.; Berge, Kjetil; Fladmark, Kari E.; Martinsen, Tom C.; Waldum, Helge; Wergedahl, Hege; Berge, Rolf K. 2003. Changed energy state and increased mitochondrial beta-oxidation rate in liver of rats associated with lowered proton electrochemical potential and stimulated uncoupling protein 2 (UCP-2) expression. Journal of Biological Chemistry. 278: 30525-30533.
  • Grav, Hans J; Tronstad, Karl Johan; Gudbrandsen, Oddrun; Berge, Kjetil; Fladmark, Kari Espolin; Martinsen, Tom C; Waldum, Helge; Wergedahl, Hege; Berge, Rolf Kristian. 2003. Changed Energy State and Increased Mitochondrial B-Oxidation Rate in Liver of Rats Associated with Lowered Proton Electrochemical Potential and Stimulated Uncoupling Protein 2 (UCP-2) Expression. Journal of Biological Chemistry. 278: 30525-30533.
  • Fladmark, Kari Espolin; Brustugun, Odd Terje; Mellgren, Gunnar; Krakstad, Camilla; Bøe, Roald; Vintermyr, Olav Karsten; Schulman, Howard; Døskeland, Stein Ove. 2002. Ca2+/calmodulin dependent protein kinase II is required for microcystin-induced apoptosis. Journal of Biological Chemistry. 277: 2804-2811.
  • Fladmark, Kari Espolin; Birkeland, Magne. 2001. Biologisk baserte blåskjelltester (BBB). Fiskehelse. 2. 26-33.
  • Mankiewicz, J; Tarczynska, M; Fladmark, Kari Espolin; Døskeland, Stein Ove; Walter, Z; Zalewski, M. 2001. Apoptotic effect of cyanobacterial extract on rat hepatocytes and human lymphocytes. Environmental Toxicology. 16: 225-233.
  • Mankiewitcz, J; Walter, Z; Tarczynska, M; Zalewski, M; Fladmark, Kari Espolin; Døskeland, Stein Ove. 2001. Apoptotic effect of cyanobacterial blooms collected from Polish water reservoirs. International Journal of Occupational Medicine and Environmental Health. 13: 335-344.
  • Serres, Margrethe Hauge; Fladmark, Kari Espolin; Døskeland, Stein Ove. 2000. An ultrasensitive competitive binding assay for the detection of protein phosphatase directed toxins. Toxicon. 38: 347-360.
  • Fladmark, Kari Espolin; Brustugun, Odd Terje; Hovland, Randi; Bøe, Ragnar; Gjertsen, Bjørn Tore; Zhivotovsky, B; Døskeland, Stein Ove. 1999. Ultrarapid apoptosis inducted by phosphatase inhibitors. Cell Death Differ. Cell Death and Differentiation. 6: 1099-1108.
  • Jensen, PH; Fladmark, Kari Espolin; Gjertsen, Bjørn Tore; Vintermyr, Olav Karsten. 1999. Caspase I related protease inhibition retards the execution of okadaic acid and camptothecin induced apoptosis and PAI-2 selective cleavage, but not commitment to cell death in HL-60 cells. British Journal of Cancer. 79: 1685-1691.
  • Serres, Margrethe Hauge; Fladmark, Kari Espolin; Døskeland, Stein Ove. 1999. An ultrasensitive competitive binding assay for the detection of toxins affecting protein phosphatases. Toxicon. 38: 347-360.
  • Brustugun, Odd Terje; Fladmark, Kari Espolin; Døskeland, Stein Ove; Orrenius, S.; Zhivotovsky, B. 1998. Apoptosis induced by microinjection of cytochrome c is caspase-dependent and is inibited by Bcl-2. Cell Death and Differentiation. 5: 660-668.
  • Fladmark, Kari Espolin; Serres, Margrethe Hauge; Larsen, Nina Lied; Yasumoto, T.; Aune, T.; Døskeland, Stein Ove. 1998. Sensitive detection of apoptogenic toxins in suspension cultures of rat and salmon hepatocytes. Toxicon. 36: 1101-1114.
  • Fladmark, Kari Espolin; Gjertsen, Bjørn Tore; Døskeland, Stein Ove; Vintermyr, Olav Karsten. 1997. Fas/APO-1 (CD95)-Induced Apoptosis of Primary Hepatocytes Is Inhibited by cAMP. Biochemical and Biophysical Research Communications - BBRC. 232: 20-25.
  • Fladmark, Kari Espolin; Gjertsen, Bjørn Tore; Molven, Anders; Mellgren, Gunnar; Vintermyr, Olav Karsten; Døskeland, Stein Ove. 1997. Gap junctions and growth control in liver regeneration and in isolated rat hepatocytes. Hepatology. 25: 847-855.
  • Zom, M; Fladmark, Kari Espolin; Øgreid, D.; Jastorff, B; Døskeland, SO; Dostman, WRG. 1995. Ala%3%3%5 is essential for high-affinity cAMP-binding of both sites A and B of cAMP-dependent protein kinase type I. FEBS Letters. 362: 291-294.
  • Zorn, M; Fladmark, Kari Espolin; Øgreid, D.; Jastorff, B; Døskeland, SO; Dostmann, WRG. 1995. ALA-335 is essential for high-affinity cAMP-binding of both sites A and B of cAMP-dependent protein kinase type I. FEBS Letters. 362: 291-294.
Rapporter/avhandlinger
  • Rungruangsak-Torrissen, Krisna; Fismen, Lise; Garberg, Hilde Kristin; Satake, Masayuki; Fladmark, Kari Espolin. 2006. Shellfish toxin azaspiracid-1 induced changes in cytoskeletal proteins in neuronal cells. Institute of Marine Research, Matre Research Station,, Institute of Marine Research and University of Bergen. 28 sider.
  • Rungruangsak-Torrissen, Krisna; Garberg, Hilde Kristin; Thorsen, Anders; Kjesbu, Olav Sigurd; Fladmark, Kari Espolin. 2006. Oocyte development in Atlantic cod (Gadus morhua L.): Trypsin-like specific activity, capacity for protein synthesis and proteomics. Institute of Marine Research, Matre Research Station,, Institute of Marine Research and University of Bergen. 29 sider.
  • Fladmark, Kari Espolin. 1998. Hepatocyte proliferation and apoptosis-regulation by cell communication and phosphorylation. Dr.scient.. -.

Se fullstendig oversikt over publikasjoner i CRIStin.

Seneste publikasjoner:

Oveland E, Gjertsen BT, Wergeland L, Selheim F, Fladmark KE, Hovland R (2008). Ligand induced Flt3-downregulation modulates cell death associated proteins and enhances chemosensitivity to idarubicin in THP-1 acute myeloid leukemia cells. Leukemia Research 33:276-87.

Solstad T., Bull V., Breivik L. and Fladmark KE (2008) Identification of protein interaction partners by immunoprecipitation; possible pitfalls and false positives. Experimental and Clinical Hepatology 4:16-22.

Solstad T, Fismen L, Garberg H and Fladmark KE (2008) Identification of a novel phosphorylation site of Acyl-CoA binding protein (ACBP) in nodularin-induced apoptotic hepatocytes. Exp. Cell. Res. 314: 2141-9.

H. Målen, F. S. Berven, K. E. Fladmark and H. G. Wiker (2007) Defining the Secreted Proteome of Mycobacterium tuberculosis by analysis of a Unique Culture Filtrate using a Mass Spectrometry Based Proteomic Profiling approach. Proteomics 7: 1702-18.

Oveland E, Fladmark KE, Wergeland L, Gjertsen BT and Hovland R (2006) Proteomic approaches to elucidate oncogenic tyrosine kinase signalling in myeloid malignancies Curr Pharm Biotechnol 7:185-198.

Solstad T and Fladmark KE (2006) Algal toxins as guidance to identify phosphoproteins with key roles in apoptotic cell death. Curr Pharm Biotechnol 7: 209-215.

Krakstad CK , Herfindal L., Gjertsen BT , Boe R , Fladmark KE , Døskeland SO (2006) CaM-kinaseII dependent commitment to microcystin-induced apoptosis is coupled to cell budding, but not to shrinkage or chromatin hypercondensation. Cell Death and Diff. 13: 1191-1202.

Dr. scient, University of Bergen. “Hepatocyte proliferation and apoptosis: regulation by cell communication and phosphorylation” (1998)

Forskergrupper

Prosjekter

Pågående prosjekter:

  • "Role of phosphorylation in regulation of redox-mediated events in apoptotic cell death" (FUGE)
  • "Nordic Network in proteomics" (NordForsk) NORPRO
  • "Kompetanseoppbygging i kvantitativ proteomikk" (Meltzer)
  • "Nordic network in quantitative proteomics" (NordForsk) Q-NORDIC