Karlsson M

References (11)

Title : Insights into the ecological generalist lifestyle of Clonostachys fungi through analysis of their predicted secretomes - Piombo_2023_Front.Microbiol_14_1112673
Author(s) : Piombo E , Guaschino M , Jensen DF , Karlsson M , Dubey M
Ref : Front Microbiol , 14 :1112673 , 2023
Abstract : INTRODUCTION: The fungal secretome comprise diverse proteins that are involved in various aspects of fungal lifestyles, including adaptation to ecological niches and environmental interactions. The aim of this study was to investigate the composition and activity of fungal secretomes in mycoparasitic and beneficial fungal-plant interactions. METHODS: We used six Clonostachys spp. that exhibit saprotrophic, mycotrophic and plant endophytic lifestyles. Genome-wide analyses was performed to investigate the composition, diversity, evolution and gene expression of Clonostachys secretomes in relation to their potential role in mycoparasitic and endophytic lifestyles. RESULTS AND DISCUSSION: Our analyses showed that the predicted secretomes of the analyzed species comprised between 7 and 8% of the respective proteomes. Mining of transcriptome data collected during previous studies showed that 18% of the genes encoding predicted secreted proteins were upregulated during the interactions with the mycohosts Fusarium graminearum and Helminthosporium solani. Functional annotation of the predicted secretomes revealed that the most represented protease family was subclass S8A (11-14% of the total), which include members that are shown to be involved in the response to nematodes and mycohosts. Conversely, the most numerous lipases and carbohydrate-active enzyme (CAZyme) groups appeared to be potentially involved in eliciting defense responses in the plants. For example, analysis of gene family evolution identified nine CAZyme orthogroups evolving for gene gains (p >= 0.05), predicted to be involved in hemicellulose degradation, potentially producing plant defense-inducing oligomers. Moreover, 8-10% of the secretomes was composed of cysteine-enriched proteins, including hydrophobins, important for root colonization. Effectors were more numerous, comprising 35-37% of the secretomes, where certain members belonged to seven orthogroups evolving for gene gains and were induced during the C. rosea response to F. graminearum or H. solani. Furthermore, the considered Clonostachys spp. possessed high numbers of proteins containing Common in Fungal Extracellular Membranes (CFEM) modules, known for their role in fungal virulence. Overall, this study improves our understanding of Clonostachys spp. adaptation to diverse ecological niches and establishes a basis for future investigation aiming at sustainable biocontrol of plant diseases.
ESTHER : Piombo_2023_Front.Microbiol_14_1112673
PubMedSearch : Piombo_2023_Front.Microbiol_14_1112673
PubMedID: 36876087

Title : Succinate prodrugs in combination with atropine and pralidoxime protect cerebral mitochondrial function in a rodent model of acute organophosphate poisoning - Piel_2022_Sci.Rep_12_20329
Author(s) : Piel S , Janowska JI , Ward JL , McManus MJ , Jose JS , Starr J , Sheldon M , Clayman CL , Elmer E , Hansson MJ , Jang DH , Karlsson M , Ehinger JK , Kilbaugh TJ
Ref : Sci Rep , 12 :20329 , 2022
Abstract : Pesticides account for hundreds of millions of cases of acute poisoning worldwide each year, with organophosphates (OPs) being responsible for the majority of all pesticide-related deaths. OPs inhibit the enzyme acetylcholinesterase (AChE), which leads to impairment of the central- and peripheral nervous system. Current standard of care (SOC) alleviates acute neurologic-, cardiovascular- and respiratory symptoms and reduces short term mortality. However, survivors often demonstrate significant neurologic sequelae. This highlights the critical need for further development of adjunctive therapies with novel targets. While the inhibition of AChE is thought to be the main mechanism of injury, mitochondrial dysfunction and resulting metabolic crisis may contribute to the overall toxicity of these agents. We hypothesized that the mitochondrially targeted succinate prodrug NV354 would support mitochondrial function and reduce brain injury during acute intoxication with the OP diisopropylfluorophosphate (DFP). To this end, we developed a rat model of acute DFP intoxication and evaluated the efficacy of NV354 as adjunctive therapy to SOC treatment with atropine and pralidoxime. We demonstrate that NV354, in combination with atropine and pralidoxime therapy, significantly improved cerebral mitochondrial complex IV-linked respiration and reduced signs of brain injury in a rodent model of acute DFP exposure.
ESTHER : Piel_2022_Sci.Rep_12_20329
PubMedSearch : Piel_2022_Sci.Rep_12_20329
PubMedID: 36434021

Title : Mitochondrial respiratory chain complex I dysfunction induced by N-methyl carbamate ex vivo can be alleviated with a cell-permeable succinate prodrug Carbamate toxicity and treatment - Janowska_2020_Toxicol.In.Vitro__104794
Author(s) : Janowska JI , Piel S , Saliba N , Kim CD , Jang DH , Karlsson M , Kilbaugh TJ , Ehinger JK
Ref : Toxicol In Vitro , :104794 , 2020
Abstract : Human exposure to carbamates and organophosphates poses a serious threat to society and current pharmacological treatment is solely targeting the compounds' inhibitory effect on acetylcholinesterase. This toxicological pathway, responsible for acute symptom presentation, can be counteracted with currently available therapies such as atropine and oximes. However, there is still significant long-term morbidity and mortality. We propose mitochondrial dysfunction as an additional cellular mechanism of carbamate toxicity and suggest pharmacological targeting of mitochondria to overcome acute metabolic decompensation. Here, we investigated the effects on mitochondrial respiratory function of N-succinimidyl N-methylcarbamate (NSNM), a surrogate for carbamate insecticides ex vivo in human platelets. Characterization of the mitochondrial toxicity of NSNM in platelets revealed a dose depended decrease in oxygen consumption linked to respiratory chain complex I while the pathway through complex II was unaffected. In intact platelets, an increase in lactate production was seen, due to a compensatory shift towards anaerobic metabolism. Treatment with a cell-permeable succinate prodrug restored the NSNM-induced (100muM) decrease in oxygen consumption and normalized lactate production to the level of control. We have demonstrated that carbamate-induced mitochondrial complex I dysfunction can be alleviated with a mitochondrial targeted countermeasure: a cell-permeable prodrug of the mitochondrial complex II substrate succinate.
ESTHER : Janowska_2020_Toxicol.In.Vitro__104794
PubMedSearch : Janowska_2020_Toxicol.In.Vitro__104794
PubMedID: 32057835

Title : Hyperpolarized [1,3-13C2 ]ethyl acetoacetate is a novel diagnostic metabolic marker of liver cancer - Jensen_2015_Int.J.Cancer_136_E117
Author(s) : Jensen PR , Serra SC , Miragoli L , Karlsson M , Cabella C , Poggi L , Venturi L , Tedoldi F , Lerche MH
Ref : International Journal of Cancer , 136 :E117 , 2015
Abstract : An increased prevalence of liver diseases such as hepatitis C and nonalcoholic fatty liver results in an augmented incidence of the most common form of liver cancer, hepatocellular carcinoma (HCC). HCC is most often found in the cirrhotic liver and it can therefore be challenging to rely on anatomical information alone when diagnosing HCC. Valuable information on specific cellular metabolism can be obtained with high sensitivity thanks to an emerging magnetic resonance (MR) technique that uses 13C labeled hyperpolarized molecules. Our interest was to explore potential new high contrast metabolic markers of HCC using hyperpolarized 13C-MR. This work led to the identification of a class of substrates, low molecular weight ethyl-esters, which showed high specificity for carboxyl esterases and proved in many cases to possess good properties for signal enhancement. In particular, hyperpolarized [1,3-13C2 ]ethyl acetoacetate (EAA) was shown to provide a metabolic fingerprint of HCC. Using this substrate a liver cancer implanted in rats was diagnosed as a consequence of an approximately 4 times higher metabolic substrate-to-product ratio than in the surrounding healthy tissue, (p=0.009). Unregulated cellular uptake as well as cosubstrate independent enzymatic conversion of EAA, made this substrate highly useful as a hyperpolarized 13C-MR marker. This could be appreciated by the signal-to-noise (SNR) obtained from EAA, which was comparable to the SNR reported in a literature liver cancer study with state-of-the-art hyperpolarized substrate, [1-13C]pyruvate. Also, the contrast-to-noise (CNR) in the EAA based metabolic ratio images was significantly improved compared with the CNR in equivalent images reported using [1-13C]pyruvate.
ESTHER : Jensen_2015_Int.J.Cancer_136_E117
PubMedSearch : Jensen_2015_Int.J.Cancer_136_E117
PubMedID: 25156718

Title : Zearalenone detoxification by zearalenone hydrolase is important for the antagonistic ability of Clonostachys rosea against mycotoxigenic Fusarium graminearum - Kosawang_2014_Fungal.Biol_118_364
Author(s) : Kosawang C , Karlsson M , Velez H , Rasmussen PH , Collinge DB , Jensen B , Jensen DF
Ref : Fungal Biol , 118 :364 , 2014
Abstract : The fungus Clonostachys rosea is antagonistic against plant pathogens, including Fusarium graminearum, which produces the oestrogenic mycotoxin zearalenone (ZEA). ZEA inhibits other fungi, and C. rosea can detoxify ZEA through the enzyme zearalenone lactonohydrolase (ZHD101). As the relevance of ZEA detoxification for biocontrol is unknown, we studied regulation and function of ZHD101 in C. rosea. Quantitative reverse-transcription PCR revealed zhd101 gene expression in all conditions studied and demonstrated dose-dependent induction by ZEA. Known inducers of the Polyketide Synthase pathway did not induce zhd101 expression, suggesting specificity of the enzyme towards ZEA. To assess the role of ZHD101 during biocontrol interactions, we generated two Deltazhd101 mutants incapable of ZEA-detoxification and confirmed their defect in degrading ZEA by HPLC. The Deltazhd101 mutants displayed a lower in vitro ability to inhibit growth of the ZEA-producing F. graminearum (strain 1104-14) compared to the wild type. In contrast, all three C. rosea strains equally inhibited growth of the F. graminearum mutant (DeltaPKS4), which is impaired in ZEA-production. Furthermore, the Deltazhd101 mutants failed to protect wheat seedlings against foot rot caused by the ZEA-producing F. graminearum. These data show that ZEA detoxification by ZHD101 is important for the biocontrol ability of C. rosea against F. graminearum.
ESTHER : Kosawang_2014_Fungal.Biol_118_364
PubMedSearch : Kosawang_2014_Fungal.Biol_118_364
PubMedID: 24742831
Gene_locus related to this paper: biooc-ZHD101

Title : Insight into trade-off between wood decay and parasitism from the genome of a fungal forest pathogen - Olson_2012_New.Phytol_194_1001
Author(s) : Olson A , Aerts A , Asiegbu F , Belbahri L , Bouzid O , Broberg A , Canback B , Coutinho PM , Cullen D , Dalman K , Deflorio G , van Diepen LT , Dunand C , Duplessis S , Durling M , Gonthier P , Grimwood J , Fossdal CG , Hansson D , Henrissat B , Hietala A , Himmelstrand K , Hoffmeister D , Hogberg N , James TY , Karlsson M , Kohler A , Kues U , Lee YH , Lin YC , Lind M , Lindquist E , Lombard V , Lucas S , Lunden K , Morin E , Murat C , Park J , Raffaello T , Rouze P , Salamov A , Schmutz J , Solheim H , Stahlberg J , Velez H , de Vries RP , Wiebenga A , Woodward S , Yakovlev I , Garbelotto M , Martin F , Grigoriev IV , Stenlid J
Ref : New Phytol , 194 :1001 , 2012
Abstract : Parasitism and saprotrophic wood decay are two fungal strategies fundamental for succession and nutrient cycling in forest ecosystems. An opportunity to assess the trade-off between these strategies is provided by the forest pathogen and wood decayer Heterobasidion annosum sensu lato. We report the annotated genome sequence and transcript profiling, as well as the quantitative trait loci mapping, of one member of the species complex: H. irregulare. Quantitative trait loci critical for pathogenicity, and rich in transposable elements, orphan and secreted genes, were identified. A wide range of cellulose-degrading enzymes are expressed during wood decay. By contrast, pathogenic interaction between H. irregulare and pine engages fewer carbohydrate-active enzymes, but involves an increase in pectinolytic enzymes, transcription modules for oxidative stress and secondary metabolite production. Our results show a trade-off in terms of constrained carbohydrate decomposition and membrane transport capacity during interaction with living hosts. Our findings establish that saprotrophic wood decay and necrotrophic parasitism involve two distinct, yet overlapping, processes.
ESTHER : Olson_2012_New.Phytol_194_1001
PubMedSearch : Olson_2012_New.Phytol_194_1001
PubMedID: 22463738
Gene_locus related to this paper: 9homo-w4jrb9 , 9homo-w4jsg4 , 9homo-w4kds7 , 9homo-w4jwl9 , 9homo-w4kjy2 , 9homo-w4jw43 , 9homo-w4ka20 , 9homo-w4k8t3 , 9homo-w4jz43 , 9homo-w4k8q2 , 9homo-w4k910 , 9homo-w4k6f5 , 9homo-w4k6j3 , 9homo-w4k8n2 , 9homo-w4jrf3 , 9homo-w4ke07 , 9homo-w4k3i8 , 9homo-w4jqh1 , 9agam-w4k203 , 9agam-w4jpy3 , 9agam-w4jn81 , 9agam-w4jmz2

Title : Dynamics of hepatic enzyme activity following birth asphyxia - Karlsson_2006_Acta.Paediatr_95_1405
Author(s) : Karlsson M , Blennow M , Nemeth A , Winbladh B
Ref : Acta Paediatr , 95 :1405 , 2006
Abstract : AIM: To investigate: 1) the occurrence of hypoxic hepatitis in full-term infants after birth asphyxia, 2) the temporal enzyme pattern in asphyxiated newborn infants, and 3) whether the degree of hypoxic hepatitis, as reflected by the rise in aminotransferase, correlates with the severity of the asphyxia and CNS symptomatology.
METHODS: Serum aminotransferases, lactate dehydrogenase, gamma-glutamyl transferase, total and conjugated bilirubin, cholinesterase activity, albumin, international normalized ratio (INR), and nucleated red blood cell count were prospectively measured in full-term asphyxiated newborn infants (n=26). Samples were collected three times during the first 72 h and once between days 6 and 12 after birth. Samples from healthy newborns (n=56), collected 24-172 h after birth, served as controls.
RESULTS: In 12 of the 26 asphyxiated infants, a serum alanine aminotransferase (S-ALAT) pattern compatible with hypoxic hepatitis was found. Five infants showed increased S-ALAT activity but with a different pattern. Similar patterns were seen in serum aspartate aminotransferase (S-ASAT). S-ALAT and -ASAT concentrations 0-72 h after birth correlated significantly with severity of hypoxic-ischaemic encephalopathy. CONCLUSION: Birth asphyxia can induce an enzyme pattern in serum compatible to hypoxic hepatitis. There seems to be a correlation between aminotransferases in serum and the extent of CNS injury.
ESTHER : Karlsson_2006_Acta.Paediatr_95_1405
PubMedSearch : Karlsson_2006_Acta.Paediatr_95_1405
PubMedID: 17062468

Title : Exon-intron organization and chromosomal localization of the mouse monoglyceride lipase gene - Karlsson_2001_Gene_272_11
Author(s) : Karlsson M , Reue K , Xia YR , Lusis AJ , Langin D , Tornqvist H , Holm C
Ref : Gene , 272 :11 , 2001
Abstract : Monoglyceride lipase (MGL) functions together with hormone-sensitive lipase to hydrolyze intracellular triglyceride stores of adipocytes and other cells to fatty acids and glycerol. In addition, MGL presumably complements lipoprotein lipase in completing the hydrolysis of monoglycerides resulting from degradation of lipoprotein triglycerides. Cosmid clones containing the mouse MGL gene were isolated from a genomic library using the coding region of the mouse MGL cDNA as probe. Characterization of the clones obtained revealed that the mouse gene contains the coding sequence for MGL on seven exons, including a large terminal exon of approximately 2.6 kb containing the stop codon and the complete 3' untranslated region. Two different 5' leader sequences, diverging 21 bp upstream of the predicted translation initiation codon, were isolated from a mouse adipocyte cDNA library. Western blot analysis of different mouse tissues revealed protein size heterogeneities. The amino acid sequence derived from human MGL cDNA clones showed 84% identity with mouse MGL. The mouse MGL gene was mapped to chromosome 6 in a region with known homology to human chromosome 3q21.
ESTHER : Karlsson_2001_Gene_272_11
PubMedSearch : Karlsson_2001_Gene_272_11
PubMedID: 11470505
Gene_locus related to this paper: human-MGLL , mouse-MGLL

Title : Expression, purification, and characterization of histidine-tagged mouse monoglyceride lipase from baculovirus-infected insect cells - Karlsson_2000_Protein.Expr.Purif_18_286
Author(s) : Karlsson M , Tornqvist H , Holm C
Ref : Protein Expr Purif , 18 :286 , 2000
Abstract : Monoglyceride lipase (MGL) has been produced with the baculovirus-insect cell system. The mouse MGL cDNA was subcloned into a baculovirus transfer vector in frame with a sequence encoding an N-terminal stretch of six histidine residues. Purification to apparent homogeneity was obtained by nickel-chelating chromatography. The final yield was 3 mg of pure enzymatically active MGL per liter of Sf9 cell suspension culture. Analysis by SDS-PAGE and mass spectrometry showed that the recombinant histidine-tagged enzyme had the expected molecular mass. With monoolein as substrate, the specific activity and the apparent K(m) were close to those of rat MGL of adipose tissue.
ESTHER : Karlsson_2000_Protein.Expr.Purif_18_286
PubMedSearch : Karlsson_2000_Protein.Expr.Purif_18_286
PubMedID: 10733881

Title : cDNA cloning, tissue distribution, and identification of the catalytic triad of monoglyceride lipase. Evolutionary relationship to esterases, lysophospholipases, and haloperoxidases - Karlsson_1997_J.Biol.Chem_272_27218
Author(s) : Karlsson M , Contreras JA , Hellman U , Tornqvist H , Holm C
Ref : Journal of Biological Chemistry , 272 :27218 , 1997
Abstract : Monoglyceride lipase catalyzes the last step in the hydrolysis of stored triglycerides in the adipocyte and presumably also complements the action of lipoprotein lipase in degrading triglycerides from chylomicrons and very low density lipoproteins. Monoglyceride lipase was cloned from a mouse adipocyte cDNA library. The predicted amino acid sequence consisted of 302 amino acids, corresponding to a molecular weight of 33,218. The sequence showed no extensive homology to other known mammalian proteins, but a number of microbial proteins, including two bacterial lysophospholipases and a family of haloperoxidases, were found to be distantly related to this enzyme. By means of multiple sequence alignment and secondary structure prediction, the structural elements in monoglyceride lipase, as well as the putative catalytic triad, were identified. The residues of the proposed triad, Ser-122, in a GXSXG motif, Asp-239, and His-269, were confirmed by site-directed mutagenesis experiments. Northern blot analysis revealed that monoglyceride lipase is ubiquitously expressed among tissues, with a transcript size of about 4 kilobases.
ESTHER : Karlsson_1997_J.Biol.Chem_272_27218
PubMedSearch : Karlsson_1997_J.Biol.Chem_272_27218
PubMedID: 9341166
Gene_locus related to this paper: mouse-MGLL , ratno-MGLL

Title : Hormone-sensitive lipase is structurally related to acetylcholinesterase, bile salt-stimulated lipase, and several fungal lipases. Building of a three-dimensional model for the catalytic domain of hormone-sensitive lipase - Contreras_1996_J.Biol.Chem_271_31426
Author(s) : Contreras JA , Karlsson M , Osterlund T , Laurell H , Svensson A , Holm C
Ref : Journal of Biological Chemistry , 271 :31426 , 1996
Abstract : Hormone-sensitive lipase is the key enzyme in the mobilization of fatty acids from adipose tissue, thereby playing a crucial role in the overall energy homeostasis in mammals. Its activity is stimulated by catecholamines through cAMP-dependent phosphorylation of a single serine, a process that is prevented by insulin. This regulatory property is unique to this enzyme among all known lipases and has been acquired during evolution through insertion of a regulatory module into an ancestral lipase. Sequence alignments have failed to detect significant homology between hormone-sensitive lipase and the rest of the mammalian lipases and esterases, to which this enzyme is only very distantly related. In the present work, we report the finding of a remarkable secondary structure homology between hormone-sensitive lipase and the enzymes from a superfamily of esterases and lipases that includes acetylcholinesterase, bile salt-stimulated lipase, and several fungal lipases. This finding, based on the identification of the secondary structure elements in the hormone-sensitive lipase sequence, has allowed us to construct a three-dimensional model for the catalytic domain of hormone-sensitive lipase. The model reveals the topological organization, predicts the components of the catalytic triad, suggests a three-dimensional localization of the regulatory module, and provides a valuable tool for the future study of structural and functional aspects of this metabolically important enzyme.
ESTHER : Contreras_1996_J.Biol.Chem_271_31426
PubMedSearch : Contreras_1996_J.Biol.Chem_271_31426
PubMedID: 8940153