Arbeidsoppgaver
- CRIStin fakultetssuperbruker
- Bibliometrianalyser (CRIStin, SciVal mfl.) og rapportering
- Forskningsinfrastruktur og kjernefasiliteter
- Verneombud, Det medisinske fakultet Sogn Arena
- Bistand og rådgivning til enkeltforskere, institutter og fakultetet knyttet til EU-prosjekter og annen ekstern finansiering
- Rådgivning i forhold til søknadsarbeidet, rammeverk, prosedyrer og budsjett
- Informasjonsarbeid, nettpublisering
- Kontaktpunkt for Institutt for medisinske basalfag og Norsk senter for molekylærmedisin i forbindelse med ekstern forskningsfinansiering innenfor EU
Bakgrunn
- Dr.philos. (fagfelt: Cellebiologi / autofagi / proteinkjemi / proteomikk), Det medisinske fakultet, UiO (2004)
- Cand. scient., Biokjemisk institutt, UiO (1994)
- Afsnitschef for Fraktioneringsafdelingen, Statens seruminstitut, København (1994-1995)
- Forskererfaring fra Det norske radiumhospital (1995-2006). Forskningsområdene omfatter blant annet kartlegging av intracellulær signaloverføringsveier i regulering av autofagi i rottehepatocytter, samt ved PDT-indusert apoptose i ulike karsinome cellelinjer. Dessuten arbeidet med utvikling av ulike proteinkinase-array scrennings-systemer.
- Læreutdanning fra Universitetet for miljø- og biovitenskap, UMB (2009)
- Lærererfaring fra videregående skole (2008-2012)
Emneord:
Forskningsadministrasjon,
Forskerutdanning,
Cristin,
analyse,
Rapportering,
Utvalget for legers videre- og etterutdanning,
Nasjonalt publiseringsråd for medisin,
kjernefasiliteter,
forskningsinfrastruktur,
Forskerstøtte MED,
Verneombud MED,
Ekstern finansiering EU
Publikasjoner
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Eggen, Ingegerd; Møller, Michael T. N; Shahzidi, Susan; Nesland, Jahn M & Qian, Peng
(2006).
Involvement of both caspase-dependent and -independent pathways in apoptotic induction by hexaminolevulinate-mediated photodynamic therapy in human lymphoma cells.
Apoptosis.
ISSN 1360-8185.
11(11),
s. 2031–2042.
doi:
10.1007/s10495-006-0190-x.
-
Eggen, Ingegerd; Shahzidi, Susan; Luksiene, Zivile; Møller, Michael T. N; Borgen, Elin & Morgan, Janet
[Vis alle 9 forfattere av denne artikkelen]
(2005).
Targeting PBR by hexaminolevulinate-mediated photodynamic therapy induces apoptosis through translocation of apoptosis-inducing factor in human leukemia cells.
Cancer Research.
ISSN 0008-5472.
65(23),
s. 11051–11060.
doi:
10.1158/0008-5472.CAN-05-0510.
Vis sammendrag
Photodynamic therapy (PDT) with endogenous protoporphyrin IX derived from 5-aminolevulinic acid or its derivatives has been established for treatments of several premalignancies and malignancies; however, the mechanism of the modality is not fully elucidated. The mitochondrial permeability transition pore consists mainly of the mitochondrial outer membrane voltage-dependent anion channel and the peripheral benzodiazepine receptor (PBR) and the mitochondrial inner membrane adenine nucleotide translocator (ANT). These mitochondrial proteins are responsible for the permeability transition that leads to apoptosis. In the present study, the human leukemia cell line, Reh, was treated with PDT using hexaminolevulinate (HAL). More than 80% of apoptotic Reh cells were found after HAL-mediated PDT (HAL-PDT) with high-molecular-weight (50 kbp) DNA fragmentation. Addition of PK11195 or Ro5-4864, two ligands of PBR, during HAL-PDT significantly inhibited the apoptotic effect. Bongkrekic acid, a ligand for ANT, also reduced the PDT effect. Although the mitochondrial transmembrane potential collapsed, neither cytosolic translocation of mitochondrial cytochrome c nor activation of caspase-9, caspase-8, caspase-3, and poly(ADP-ribose) polymerase were found. However, nuclear translocation of mitochondrial apoptosis-inducing factor (AIF) was shown by both immunoblotting and immunocytochemistry. Because AIF is the sole one among all proapoptotic factors involved in caspase-dependent and caspase-independent pathways that induces the high-molecular-weight DNA fragmentation, we conclude that HAL-PDT specifically targets PBR, leading to apoptosis of the Reh cells through nuclear translocation of mitochondrial AIF. This study suggests PBR as a possible novel therapeutic target for HAL-based PDT of cancer.
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Samari, Hamid Reza; Møller, Michael T. N; Holden, Lise; Asmyhr, Tonje & Seglen, Per O.
(2005).
Biochem. J. (2005) 386, 237–244 (Printed in Great Britain) 237
Stimulation of hepatocytic AMP-activated protein kinase by okadaic acid and other autophagy-suppressive toxins.
Biochemical Journal.
ISSN 0264-6021.
386,
s. 237–244.
doi:
10.1042/BJ20040609.
Vis sammendrag
Autophagic activity in isolated rat hepatocytes is strongly suppressed by OA (okadaic acid) and other PP (protein phosphatase)-inhibitory toxins as well as by AICAR (5-aminoimidazole-4-carboxamide riboside), a direct activator of AMPK (AMP-activated protein kinase). To investigate whether AMPK is a mediator of the effects of the toxin, a phosphospecific antibody directed against the activation of phosphorylation of the AMPK α (catalytic)-subunit at Thr172 was used to assess the activation status of this enzyme. AICAR as well as all the toxins tested (OA, microcystin-LR, calyculin A, cantharidin and tautomycin) induced strong, dose-dependent AMPKα phosphorylation, correlating with AMPK activity in situ (in intact hepatocytes) as measured by the AMPK-dependent phosphorylation of acetyl-CoA carboxylase at Ser79. All treatments induced the appearance of multiple, phosphatase-sensitive, low-mobility forms of the AMPK α-subunit, consistent with phosphorylation at several sites other than Thr172. The flavonoid naringin, an effective antagonist of OA-induced autophagy suppression, inhibited the AMPK phosphorylation and mobility shifting induced by AICAR, OA or microcystin, but not the changes induced by calyculin A or cantharidin. AMPK may thus be activated both by a naringin-sensitive and a naringin-resistant mechanism, probably involving the PPs PP2A and PP1 respectively. Neither the Thr172-phosphorylating protein kinase LKB1 nor the Thr172-dephosphorylating PP, PP2C, were mobility-shifted after treatment with toxins or AICAR, whereas a slight mobility shifting of the regulatory AMPK β-subunit was indicated. Immunoblotting with a phosphospecific antibody against pSer108 at the β-subunit revealed a naringin-sensitive phosphorylation induced by OA, microcystin and AICAR and a naringin-resistant phosphorylation induced by calyculin A and cantharidin, suggesting that β-subunit phosphorylation could play a role in AMPK activation. Naringin antagonized the autophagy-suppressive effects of AICAR and OA, but not the autophagy suppression caused by cantharidin, consistent with AMPK-mediated inhibition of autophagy by toxins as well as by AICAR.
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Møller, Michael T. N; Samari, Hamid R. & Seglen, Per O.
(2004).
Toxin-induced tail phosphorylation of hepatocellular S6 kinase: Evidence for a dual involvement of the AMP-activated protein kinase in S6 kinase regulation.
Toxicological Sciences.
ISSN 1096-6080.
s. 628–637.
doi:
10.1093/toxsci/kfh273.
Vis sammendrag
Several protein phosphatase-inhibitory toxins (okadaic acid, microcystin, calyculin A, cantharidin, tautomycin) administered to isolated rat hepatocytes were found to induce phosphorylation in the tail region of S6 kinase (S6K; p70S6K1) as detected with a phosphospecific antibody against doubly phosphorylated Thr-421/Ser424. 5-Aminoimidazole-4-carboxamide riboside (AICAR), an adenosine analogue that elicits activation of the hepatocellular AMP-activated protein kinase (AMPK), similarly stimulated S6K tail phosphorylation. The flavonoid naringin prevented the effects of AICAR, okadaic acid, and microcystin on AMPK activation as well as on S6K tail phosphorylation, suggesting AMPK as a mediator of the latter. The effects of AICAR and the toxins were rapamycin resistant; in contrast, amino acids induced an S6K tail phosphorylation that was rapamycin sensitive, suggesting mediation by the protein kinase mammalian target of rapamycin (mTOR). Amino acids activated S6K by phosphorylation at Thr-389, but the toxins did not, and AICAR in fact suppressed the activating phosphorylation induced by the amino acids. The possibility thus must be considered that the phosphorylated S6K tail may transmit a toxin-induced signal independently of S6K enzymatic activity. Despite their inability to activate S6K, the toxins (but not AICAR) stimulated phosphorylation of the ribosomal protein S6, presumably by activating some other S6-phosphorylating protein kinase.
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Møller, Michael T. N; Samari, Hamid R.; Fengsrud, Monica ; Strømhaug, Per E.; Østvold, Anne C. & Seglen, Per O.
(2003).
Okadaic acid-induced, naringin-sensitive phosphorylation of glycine N-methyltransferase in isolated rat hepatocytes.
Biochemical Journal.
ISSN 0264-6021.
373,
s. 505–513.
doi:
10.1042/BJ20030502.
Vis sammendrag
Glycine N-methyltransferase (GNMT) is an abundant cytosolic enzyme that catalyses the methylation of glycine into sarcosine, coupled with conversion of the methyl donor, S -adenosylmethionine (AdoMet), into S -adenosylhomocysteine (AdoHcy). GNMT is believed to play a role in monitoring the AdoMet/AdoHcy ratio, and hence the cellular methylation capacity, but regulation of the enzyme itself is not well understood. In the present study, treatment of isolated rat hepatocytes with the protein phosphatase inhibitor okadaic acid, was found to induce an overphosphorylation of GNMT, as shown by proteomic analysis. The analysis comprised two-dimensional gel electrophoretic separation of (32)P-labelled phosphoproteins and identification of individual protein spots by matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry. The identity of GNMT was verified by N-terminal Edman sequencing of tryptic peptides. Chromatographic separation of proteolytic peptides and (32)P-labelled amino acids suggested that GNMT was phosphorylated within a limited region, and only at serine residues. GNMT phosphorylation could be suppressed by naringin, an okadaic acid-antagonistic flavonoid. To assess the possible functional role of GNMT phosphorylation, the effect of okadaic acid on hepatocytic AdoMet and AdoHcy levels was examined, using HPLC separation for metabolite analysis. Surprisingly, okadaic acid was found to have no effect on the basal levels of AdoMet or AdoHcy. An accelerated AdoMet-AdoHcy flux, induced by the addition of methionine (1 mM), was likewise unaffected by okadaic acid. 5-Aminoimidazole-4-carboxamide riboside, an activator of the hepatocytic AMP-activated protein kinase, similarly induced GNMT phosphorylation without affecting AdoMet and AdoHcy levels. Activation of cAMP-dependent protein kinase by dibutyryl-cAMP, reported to cause GNMT phosphorylation under cell-free conditions, also had little effect on hepatocytic AdoMet and AdoHcy levels. Phosphorylation of GNMT would thus seem to play no role in regulation of the intracellular AdoMet/AdoHcy ratio, but could be involved in other GNMT functions, such as the binding of folates or aromatic hydrocarbons.
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Ruud Larsen, Ann K.; Møller, Michael T. N; Blankson, Henrietta; Samari, Hamid R.; Holden, Lise & Seglen, Per O.
(2002).
Naringin-sensitive phosphorylation of plectin, a cytoskeletal cross-linking protein, in isolated rat hepatocytes.
Journal of Biological Chemistry.
ISSN 0021-9258.
277,
s. 34826–34835.
doi:
10.1074/jbc.M205028200.
Fulltekst i vitenarkiv
Vis sammendrag
To identify phosphoproteins that might play a role in naringin-sensitive hepatocellular cytoskeletal disruption and apoptosis induced by algal toxins, hepatocyte extracts were separated by gel electrophoresis and immunostained with a phosphothreonine-directed antibody. Use of dilute (5%) polyacrylamide gels containing 6 m urea allowed the resolution of one very large (approximately 500-kDa) okadaic acid- and naringin-sensitive phosphoprotein, identified by tryptic fingerprinting, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and immunostaining as the cytolinker protein, plectin. The naringin-sensitive phosphorylation induced by okadaic acid and microcystin-LR probably reflected inhibition of a type 2A protein phosphatase, whereas the naringin-resistant phosphorylation induced by calyculin A, tautomycin, and cantharidin probably involved a type 1 phosphatase. Okadaic acid caused a collapse of the plectin-immunostaining bile canalicular sheaths and the general cytoskeletal plectin network into numerous medium-sized plectin aggregates. Inhibitors of protein kinase C, cAMP-dependent protein kinase, or Ca(2+)/calmodulin-dependent kinase II had moderate or no protective effects on plectin network disruption, whereas naringin offered 86% protection. Okadaic acid induced a naringin-sensitive phosphorylation of AMP-activated protein kinase (AMPK), the stress-activated protein kinases SEK1 and JNK, and S6 kinase. The AMPK-activating kinase (AMPKK) is likely to be the target of inhibition by naringin, the other kinases serving as downstream components of an AMPKK-initiated signaling pathway.
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Strømhaug, Per E.; Fengsrud, Monica ; Berg, Trond Olav; Møller, Michael T. N; Grotterød, Else M. & Samari, Hamid Reza
[Vis alle 12 forfattere av denne artikkelen]
(1997).
Regulation of autophagy by protein phosphorylation,
Proteolysis in cell function.
IOS Press.
s. 357–366.
Se alle arbeider i Cristin
Publisert
23. mars 2012 10:11
- Sist endret
5. okt. 2022 15:02