Blar i Department of Biomedicine på forfatter "Kleppe, Rune"
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The 14-3-3 proteins in regulation of cellular metabolism
Kleppe, Rune; Martinez, Aurora; Døskeland, Stein Ove; Haavik, Jan (Peer reviewed; Journal article, 2011-09)Thirty years ago, it was discovered that 14-3-3 proteins could activate enzymes involved in amino acid metabolism. In the following decades, 14-3-3s have been shown to be involved in many different signaling pathways that ... -
ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications
Homaei, Selina Cannon; Barone, Helene; Kleppe, Rune; Betari, Nibal; Reif, Andreas; Haavik, Jan (Journal article; Peer reviewed, 2021)Neurometabolic diseases (NMDs) are typically caused by genetic abnormalities affecting enzyme functions, which in turn interfere with normal development and activity of the nervous system. Although the individual disorders ... -
Cell Death inducing microbial protein phosphatase inhibitors-mechanisms of action
Kleppe, Rune; Herfindal, Lars; Døskeland, Stein Ove (Peer reviewed; Journal article, 2015-10-22)Okadaic acid (OA) and microcystin (MC) as well as several other microbial toxins like nodularin and calyculinA are known as tumor promoters as well as inducers of apoptotic cell death. Their intracellular targets are the ... -
Cyclic AMP can promote APL progression and protect myeloid leukemia cells against anthracycline-induced apoptosis
Gausdal, Gro; Wergeland, Anita; Skavland, Jørn; Nguyen, Eric; Pendino, Frédéric; Rouhee, Nazanin; McCormack, Emmet; Herfindal, Lars; Kleppe, Rune; Havemann, Ursula; Schwede, Frank; Bruserud, Øystein; Gjertsen, Bjørn Tore; Lanotte, Michel; Ségal-Bendirdjian, Evelyne; Døskeland, Stein Ove (Peer reviewed; Journal article, 2013)We show that cyclic AMP (cAMP) elevating agents protect blasts from patients with acute promyelocytic leukemia (APL) against death induced by first-line anti-leukemic anthracyclines like daunorubicin (DNR). The cAMP effect ... -
The effects of phenylalanine and tyrosine levels on dopamine production in rat PC12 cells. Implications for treatment of phenylketonuria, tyrosinemia type 1 and comorbid neurodevelopmental disorders
Szigetvari, Peter Daniel; Patil, Sudarshan; Birkeland, Even; Kleppe, Rune; Haavik, Jan (Journal article; Peer reviewed, 2023)Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, resulting in phenylalanine accumulation and impaired tyrosine production. In Tyrosinemia ... -
Epistatic and gene wide effects in YWHA and aromatic amino hydroxylase genes across ADHD and other common neuropsychiatric disorders: Association with YWHAE
Jacobsen, Kaya Kvarme; Kleppe, Rune; Johansson, Stefan; Zayats, Tetyana; Haavik, Jan (Peer reviewed; Journal article, 2015-09)Monoamines critically modulate neurophysiological functions affected in several neuropsychiatric disorders. We therefore examined genes encoding key enzymes of catecholamine and serotonin biosynthesis (tyrosine and tryptophan ... -
Functional studies of tyrosine hydroxylase missense variants reveal distinct patterns of molecular defects in dopa-responsive dystonia
Fossbakk, Agnete; Kleppe, Rune; Knappskog, Per; Martinez, Aurora; Haavik, Jan (Peer reviewed; Journal article, 2014-06-03)Congenital tyrosine hydroxylase deficiency (THD) is found in autosomal-recessive Dopa-responsive dystonia and related neurological syndromes. The clinical manifestations of THD are variable, ranging from early-onset lethal ... -
GADL1 is a multifunctional decarboxylase with tissue-specific roles in β-alanine and carnosine production
Mahootchi, Elaheh; Homaei, Selina Cannon; Kleppe, Rune; Winge, Ingeborg; Hegvik, Tor-Arne; Perez, Roberto Megias; Totland, Christian; Mogavero, Floriana; Baumann, Anne; Glennon, Jeffrey Colm; Miletic, Hrvoje; Kursula, Petri; Haavik, Jan (Journal article; Peer reviewed, 2020)Carnosine and related β-alanine–containing peptides are believed to be important antioxidants, pH buffers, and neuromodulators. However, their biosynthetic routes and therapeutic potential are still being debated. This ... -
Increased microvascular permeability in mice lacking Epac1 (Rapgef3)
Kopperud, Reidun Kristin; Rygh, Cecilie Brekke; Karlsen, Tine Veronica; Krakstad, Camilla; Kleppe, Rune; Høivik, Erling Andre; Bakke, Marit; Tenstad, Olav; Selheim, Frode; Liden, Åsa; Madsen, Lise; Pavlin, Tina; Taxt, Torfinn; Kristiansen, K.; Curry, FE; Reed, Rolf K.; Doskeland, Stein Ove (Peer reviewed; Journal article, 2017-02)Aim: Maintenance of the blood and extracellular volume requires tight control of endothelial macromolecule permeability, which is regulated by cAMP signalling. This study probes the role of the cAMP mediators rap guanine ... -
Introduction of aromatic ring-containing substituents in cyclic nucleotides is associated with inhibition of toxin uptake by the hepatocyte transporters OATP 1B1 and 1B3
Herfindal, Lars; Krakstad, Camilla; Myhren, Lene Elisabeth; Hagland, Hanne; Kopperud, Reidun Kristin; Teigen, Knut; Schwede, Frank; Kleppe, Rune; Døskeland, Stein Ove (Peer reviewed; Journal article, 2014-04-16)Analogs of the cyclic nucleotides cAMP and cGMP have been extensively used to mimic or modulate cellular events mediated by protein kinase A (PKA), Exchange protein directly activated by cAMP (Epac), or protein kinase G ... -
Involvement of the 14-3-3 Gene Family in Autism Spectrum Disorder and Schizophrenia: Genetics, Transcriptomics and Functional Analyses
Torrico, Bàrbara; Antón-Galindo, Ester; Fernàndez-Castillo, Noèlia; Rojo-Francàs, Eva; Ghorbani, Sadaf; Pineda-Cirera, Laura; Hervas, Amaia; Rueda, Isabel; Moreno, Estefanía; Fullerton, Janice M.; Casadó, Vicent; Buitelaar, Jan K; Rommelse, Nanda; Franke, Barbara; Reif, Andreas; Chiocchetti, Andreas G; Freitag, Christine; Kleppe, Rune; Haavik, Jan; Toma, Claudio; Cormand, Bru (Journal article; Peer reviewed, 2020)The 14-3-3 protein family are molecular chaperones involved in several biological functions and neurological diseases. We previously pinpointed YWHAZ (encoding 14-3-3ζ) as a candidate gene for autism spectrum disorder (ASD) ... -
Mammalian CSAD and GADL1 have distinct biochemical properties and patterns of brain expression
Winge, Ingeborg; Teigen, Knut; Fossbakk, Agnete; Mahootchi, Elaheh; Kleppe, Rune; Sköldberg, Filip; Kämpe, Olle; Haavik, Jan (Peer reviewed; Journal article, 2015-11)Variants in the gene encoding the enzyme glutamic acid decarboxylase like 1 (GADL1) have been associated with response to lithium therapy. Both GADL1 and the related enzyme cysteine sulfinic acid decarboxylase (CSAD) have ... -
Modelling cellular signal communication mediated by phosphorylation dependent interaction with 14-3-3 proteins
Kleppe, Rune; Ghorbani, Sadaf; Martinez, Aurora; Haavik, Jan (Peer reviewed; Journal article, 2014-01-03)The 14-3-3 proteins are important effectors of Ser/Thr phosphorylation in eukaryotic cells. Using mathematical modelling we investigated the roles of these proteins as effectors in signalling pathways that involve ... -
Personalized Medicine to Improve Treatment of Dopa-Responsive Dystonia—A Focus on Tyrosine Hydroxylase Deficiency
Nygaard, Gyrid; Szigetvari, Peter D.; Grindheim, Ann Kari; Ruoff, Peter; Martinez, Aurora; Haavik, Jan; Kleppe, Rune; Flydal, Marte I. (Journal article; Peer reviewed, 2021)Dopa-responsive dystonia (DRD) is a rare movement disorder associated with defective dopamine synthesis. This impairment may be due to the fact of a deficiency in GTP cyclohydrolase I (GTPCHI, GCH1 gene), sepiapterin ... -
Phosphorylation at serine 31 targets tyrosine hydroxylase tovesicles for transport along microtubules
Jorge Finnigan, Ana; Kleppe, Rune; K C, Kunwar Jung; Ying, Ming; Marie, Michael Bruno Eric; Rios Mondragon, Ivan; Salvatore, Michael F; Saraste, Jaakko; Martinez, Aurora (Peer reviewed; Journal article, 2017)Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine into L-DOPA, which is the rate-limiting step in the synthesis of catecholamines, such as dopamine, in dopaminergergic neurons. Low dopamine levels and death ... -
Regulation of tyrosine hydroxylase is preserved across different homo- and heterodimeric 14-3-3 proteins
Ghorbani, Sadaf; Fossbakk, Agnete; Jorge Finnigan, Ana; Flydal, Marte Innselset; Haavik, Jan; Kleppe, Rune (Peer reviewed; Journal article, 2016-05)Tyrosine hydroxylase (TH) is regulated by members of the 14-3-3 protein family. However, knowledge about the variation between 14-3-3 proteins in their regulation of TH is still limited. We examined the binding, effects ... -
Serine 19 phosphorylation and 14‐3‐3 binding regulate phosphorylation and dephosphorylation of tyrosine hydroxylase on serine 31 and serine 40
Ghorbani, Sadaf; Szigetvari, Peter Daniel; Haavik, Jan; Kleppe, Rune (Peer reviewed; Journal article, 2019-09-17)Multisite phosphorylation and structural flexibility allow for complex regulation of proteins through cellular signaling. Tyrosine hydroxylase (TH), a key enzyme of catecholamine synthesis, is regulated by multiple neuronal ... -
Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation
Bueno-Carrasco, María Teresa; Cuellar, Jorge; Flydal, Marte Innselset; Santiago, Cesar; Kråkenes, Trond-André; Kleppe, Rune; Jose R, Lopez-Blanco; Marcilla, Miguel; Teigen, Knut; Alvira, Sara; Chacón, Pablo; Martinez, Aurora; Valpuesta, José M (Journal article; Peer reviewed, 2022)Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of dopamine (DA) and other catecholamines, and its dysfunction leads to DA deficiency and parkinsonisms. Inhibition by catecholamines and ... -
Tyrosine and tryptophan hydroxylases as therapeutic targets in human disease
Waløen, Kai; Kleppe, Rune; Martinez, Aurora; Haavik, Jan (Peer reviewed; Journal article, 2017)Introduction: The ancient and ubiquitous monoamine signalling molecules serotonin, dopamine, norepinephrine, and epinephrine are involved in multiple physiological functions. The aromatic amino acid hydroxylases tyrosine ... -
Tyrosinemia Type 1 and symptoms of ADHD: Biochemical mechanisms and implications for treatment and prognosis
Barone, Helene; Bliksrud, Yngve Thomas; Elgen, Irene Bircow; Szigetvari, Peter Daniel; Kleppe, Rune; Ghorbani, Sadaf; Hansen, Eirik Vangsøy; Haavik, Jan (Peer reviewed; Journal article, 2020)Hereditary tyrosinemia Type 1 (HT‐1) is a rare metabolic disease where the enzyme catalyzing the final step of tyrosine breakdown is defect, leading to accumulation of toxic metabolites. Nitisinone inhibits the degradation ...