NORTON HEISE

Scopus Publications

Sugarcane Bagasse Polysaccharides Decomposition by the Cockroach Digestive System
D. Pagliuso, A. Grandis, D. G. Santos, C. Ferreira, W. R. Terra, C. Cardoso, A. C. Pimentel, F. J. Fuzita, J. Pereira, I. Ramos, L. Quezia, A. C. Bahia, N. Heise, M. S. Buckeridge, E. A. Machado
Bioenergy Research, 2025
Stage-specific function of sphingolipid synthases in African trypanosomes
Norton Heise, Carolina M. Koeller, Mohamed Sharif, James D. Bangs
Mbio, 2025
The protozoan parasite Trypanosoma brucei is the only known eukaryote capable of synthesizing the three main phosphosphingolipids: sphingomyelin (SM), inositol phosphorylceramide (IPC), and ethanolamine phosphorylceramide (EPC). It has four paralogous genes encoding sphingolipid synthases ( TbSLS1–4 ). TbSLS1 is a dedicated IPC synthase, TbSLS2 is a dedicated EPC synthase, and TbSLS3 and TbSLS4 are bifunctional SM/EPC synthases. IPC synthesis occurs exclusively in the procyclic insect stage (PCF), EPC is limited to the mammalian bloodstream form (BSF), and SM is synthesized throughout the life cycle. TbSLSs are indispensable for the viability of BSF and are, thus, potential drug targets. The relative stage-specific expression of each TbSLS paralog was compared, and the results match phosphosphingolipid content. Induction of pan-specific RNAi silencing was lethal in both BSF and PCF. To investigate individual TbSLS functions, separate HA-tagged genes, recoded to be RNAi-resistant (RNAi R ), were engineered to replace a single allele of the entire TbSLS locus within parental BSF and PCF RNAi cell lines. RNAi R TbSLS3 and TbSLS4 both rescued BSF growth under silencing. Expression of RNAi R TbSLS1 , normally repressed in BSF, did not rescue BSF viability but was not detrimental to normal in vitro growth. RNAi R TbSLS1 , TbSLS3 , and TbSLS4 were each sufficient to rescue PCF growth, indicating IPC is not essential for PCF viability in vitro . All TbSLSs localize to distal Golgi compartments in both BSF and PCF cells. These findings raise interesting questions about the roles of individual phosphosphingolipids in in vivo infection of the mammalian and tsetse hosts. IMPORTANCE African trypanosomes are eukaryotic pathogens that cause human and veterinary African trypanosomaisis. Uniquely, they synthesize all three major phosphosphingolipid species using four distinct sphingolipid synthases (SLS). This work details the function of each SLS in both bloodstream and insect form parasites. Novel and unexpected sphingolipid dependences are found in each stage. These results are consistent with this metabolic pathway being a valid target for chemotherapeutic intervention.
Identification and Characterization of a Glycoside Hydrolase Family 9 Member from the Digestive Gland of the Snail Achatina fulica
Youssef Bacila Sade, Camila Silva Gonçalves, Sandra Mara Naressi Scapin, Guilherme Luiz Pinheiro, Roberto Becht Flatschart, Wanderley de Souza, Norton Heise, Ednildo de Alcantara Machado
Bioenergy Research, 2022
Venom alkaloids against Chagas disease parasite: search for effective therapies
Rafael C. M. Costa Silva, Eduardo G. P. Fox, Fabio M. Gomes, Daniel F. Feijó, Isabela Ramos, Carolina M. Koeller, Tatiana F. R. Costa, Nathalia S. Rodrigues, Ana P. Lima, Georgia C. Atella, Kildare Miranda, Alejandra C. Schoijet, Guillermo D. Alonso, Ednildo de Alcântara Machado, Norton Heise
Scientific Reports, 2020
Chagas disease is an important disease affecting millions of patients in the New World and is caused by a protozoan transmitted by haematophagous kissing bugs. It can be treated with drugs during the early acute phase; however, effective therapy against the chronic form of Chagas disease has yet to be discovered and developed. We herein tested the activity of solenopsin alkaloids extracted from two species of fire ants against the protozoan parasite Trypanosoma cruzi, the aetiologic agent of Chagas disease. Although IC50 determinations showed that solenopsins are more toxic to the parasite than benznidazole, the drug of choice for Chagas disease treatment, the ant alkaloids presented a lower selectivity index. As a result of exposure to the alkaloids, the parasites became swollen and rounded in shape, with hypertrophied contractile vacuoles and intense cytoplasmic vacuolization, possibly resulting in osmotic stress; no accumulation of multiple kinetoplasts and/or nuclei was detected. Overexpressing phosphatidylinositol 3-kinase—an enzyme essential for osmoregulation that is a known target of solenopsins in mammalian cells—did not prevent swelling and vacuolization, nor did it counteract the toxic effects of alkaloids on the parasites. Additional experimental results suggested that solenopsins induced a type of autophagic and programmed cell death in T. cruzi. Solenopsins also reduced the intracellular proliferation of T. cruzi amastigotes in infected macrophages in a concentration-dependent manner and demonstrated activity against Trypanosoma brucei rhodesiense bloodstream forms, which is another important aetiological kinetoplastid parasite. The results suggest the potential of solenopsins as novel natural drugs against neglected parasitic diseases caused by kinetoplastids.
Endocytosis and Exocytosis in Leishmania amazonensis Are Modulated by Bromoenol Lactone
Anne C. S. Fernandes, Deivid C. Soares, Roberta F. C. Neves, Carolina M. Koeller, Norton Heise, Camila M. Adade, Susana Frases, José R. Meyer-Fernandes, Elvira M. Saraiva, Thaïs Souto-Padrón
Frontiers in Cellular and Infection Microbiology, 2020
In the protozoan pathogen Leishmania, endocytosis and exocytosis occur mainly in the small area of the flagellar pocket membrane, which makes this parasite an interesting model of strikingly polarized internalization and secretion. Moreover, little is known about vesicle recognition and fusion mechanisms, which are essential for both endo/exocytosis in this parasite. In other cell types, vesicle fusion events require the activity of phospholipase A2 (PLA2), including Ca2+-independent iPLA2 and soluble, Ca2+-dependent sPLA2. Here, we studied the role of bromoenol lactone (BEL) inhibition of endo/exocytosis in promastigotes of L. amazonensis. PLA2 activities were assayed in intact parasites, in whole conditioned media, and in soluble and extracellular vesicles (EVs) conditioned media fractions. BEL did not affect the viability of promastigotes, but reduced the differentiation into metacyclic forms. Intact parasites and EVs had BEL-sensitive iPLA2 activity. BEL treatment reduced total EVs secretion, as evidenced by reduced total protein concentration, as well as its size distribution and vesicles in the flagellar pocket of treated parasites as observed by TEM. Membrane proteins, such as acid phosphatases and GP63, became concentrated in the cytoplasm, mainly in multivesicular tubules of the endocytic pathway. BEL also prevented the endocytosis of BSA, transferrin and ConA, with the accumulation of these markers in the flagellar pocket. These results suggested that the activity inhibited by BEL, which is one of the irreversible inhibitors of iPLA2, is required for both endocytosis and exocytosis in promastigotes of L. amazonensis.
Tamoxifen inhibits the biosynthesis of inositolphosphorylceramide in Leishmania
Cristiana T. Trinconi, Danilo C. Miguel, Ariel M. Silber, Christopher Brown, John G.M. Mina, Paul W. Denny, Norton Heise, Silvia R.B. Uliana
International Journal for Parasitology Drugs and Drug Resistance, 2018
Previous work from our group showed that tamoxifen, an oral drug that has been in use for the treatment of breast cancer for over 40 years, is active both in vitro and in vivo against several species of Leishmania, the etiological agent of leishmaniasis. Using a combination of metabolic labeling with [ 3 H]-sphingosine and myo-[ 3 H]-inositol, alkaline hydrolysis, HPTLC fractionations and mass spectrometry analyses, we observed a perturbation in the metabolism of inositolphosphorylceramides (IPCs) and phosphatidylinositols (PIs) after treatment of L. amazonensis promastigotes with tamoxifen, with a significant reduction in the biosynthesis of the major IPCs (composed of d16:1/18:0-IPC, t16:0/C18:0-IPC, d18:1/18:0-IPC and t16:0/20:0-IPC) and PIs (sn-1-O-(C 18:0 )alkyl -2-O-(C 18:1 )acylglycerol-3-HPO 4 -inositol and sn-1-O-(C 18:0 )acyl-2-O-(C 18:1 )acylglycerol-3-HPO 4 -inositol) species. Substrate saturation kinetics of myo-inositol uptake analyses indicated that inhibition of inositol transport or availability were not the main reasons for the reduced biosynthesis of IPC and PI observed in tamoxifen treated parasites. An in vitro enzymatic assay was used to show that tamoxifen was able to inhibit the Leishmania IPC synthase with an IC 50 value of 8.48 M (95% CI 7.68-9.37), suggesting that this enzyme is most likely one of the targets for this compound in the parasites.
Antibody repertoires identify β-tubulin as a host protective parasite antigen in mice infected with Trypanosoma cruzi
Fabricio Montalvão, Danielle Oliveira Nascimento, Marise P. Nunes, Carolina M. Koeller, Alexandre Morrot, Leticia Miranda S. Lery, Paulo M. Bisch, Santuza M. R. Teixeira, Rita Vasconcellos, Leonardo Freire-de-Lima, Marcela F. Lopes, Norton Heise, George A. DosReis, Célio Geraldo Freire-de-Lima
Frontiers in Immunology, 2018
Few studies investigate the major protein antigens targeted by the antibody repertoire of mice naturally infected with Trypanosoma cruzi. To detect global IgG antibody specificities, sera from infected mice were immunoblotted against whole T. cruzi extracts. By proteomic analysis, we were able to identify the most immunogenic T. cruzi proteins. We identified three major antigens as Pyruvate phosphate dikinase, Hsp-85 and β-tubulin. The major protein band recognized by host IgG was T. cruzi β-tubulin. The T. cruzi β-tubulin gene was cloned, expressed in E. coli, and recombinant T. cruzi β-tubulin was obtained. Infection increased IgG reactivity against recombinant T. cruzi β-tubulin. A single immunization of mice with recombinant T. cruzi β-tubulin increased specific IgG reactivity, and induced protection against T. cruzi infection. These results indicate that repertoire analysis is a valid approach to identify antigens for vaccines against Chagas disease.
Plasmodium falciparum invasion and intraerythrocytic development are impaired by 2′ 3′-dialdehyde adenosine
Leandro S. Silva, Gustavo C. Prado, Paula G. Quintana, Norton Heise, Kildare R. Miranda, Eduardo J.L. Torres, Pedro M. Persechini, Ana Acacia de Sá Pinheiro, Julieta Schachter
Microbes and Infection, 2018
POM-1 inhibits P2 receptors and exhibits anti-inflammatory effects in macrophages
Gabriela Pimenta-dos-Reis, Eduardo José Lopes Torres, Paula Gabriela Quintana, Lincon Onorio Vidal, Bárbara Andréa Fortes dos Santos, Chuan-Sheng Lin, Norton Heise, Pedro Muanis Persechini, Julieta Schachter
Purinergic Signalling, 2017
H+-dependent inorganic phosphate uptake in Trypanosoma brucei is influenced by myo-inositol transporter
Thais Russo-Abrahão, Carolina Macedo Koeller, Michael E. Steinmann, Stephanie Silva-Rito, Thaissa Marins-Lucena, Michele Alves-Bezerra, Naira Ligia Lima-Giarola, Iron Francisco de-Paula, Amaia Gonzalez-Salgado, Erwin Sigel, Peter Bütikofer, Katia Calp Gondim, Norton Heise, José Roberto Meyer-Fernandes
Journal of Bioenergetics and Biomembranes, 2017
Hyperglycemia exacerbates colon cancer malignancy through hexosamine biosynthetic pathway
A Vasconcelos-dos-Santos, H F B R Loponte, N R Mantuano, I A Oliveira, I F de Paula, L K Teixeira, J C M de-Freitas-Junior, K C Gondim, N Heise, R Mohana-Borges, J A Morgado-Díaz, W B Dias, A R Todeschini
Oncogenesis, 2017
Capsular polysaccharides from Cryptococcus neoformans modulate production of neutrophil extracellular traps (NETs) by human neutrophils
Juliana D. B. Rocha, Michelle T. C. Nascimento, Debora Decote-Ricardo, Suzana Côrte-Real, Alexandre Morrot, Norton Heise, Marise P. Nunes, José Osvaldo Previato, Lucia Mendonça-Previato, George A. DosReis, Elvira M. Saraiva, Célio G. Freire-de-Lima
Scientific Reports, 2015
2′,3′-dialdehyde of ATP, ADP, and adenosine inhibit HIV-1 reverse transcriptase and HIV-1 replication
Julieta Schachter, Ana Valadao, Renato Aguiar, Victor Barreto-de-Souza, Atila Rossi, Pablo Arantes, Hugo Verli, Paula Quintana, Norton Heise, Amilcar Tanuri, Dumith Bou-Habib, Pedro Persechini
Current HIV Research, 2014
Golgi UDP-GlcNAc:Polypeptide O-α-N-Acetyl-D-Glucosaminyltransferase 2 (TcOGNT2) regulates trypomastigote production and function in Trypanosoma cruzi
Carolina M. Koeller, Hanke van der Wel, Christa L. Feasley, Fernanda Abreu, Juliana Dutra Barbosa da Rocha, Fabrício Montalvão, Patrícia Fampa, Flávia C. G. dos Reis, Georgia C. Atella, Thaís Souto-Padrón, Christopher M. West, Norton Heise
Eukaryotic Cell, 2014
Infection with Leishmania major induces a cellular stress response in macrophages
Alessandra A. Filardy, Ana Caroline Costa-da-Silva, Carolina M. Koeller, Kamila Guimarães-Pinto, Flávia L. Ribeiro-Gomes, Marcela F. Lopes, Norton Heise, Célio G. Freire-de-Lima, Marise P. Nunes, George A. DosReis
Plos One, 2014
Molecular and functional characterization of the ceramide synthase from Trypanosoma cruzi
Juliana M. Figueiredo, Deivid C. Rodrigues, Rafael C.M.C. Silva, Carolina M. Koeller, James C. Jiang, S. Michal Jazwinski, José O. Previato, Lucia Mendonça-Previato, Turán P. Ürményi, Norton Heise
Molecular and Biochemical Parasitology, 2012
The sphingolipid biosynthetic pathway is a potential target for chemotherapy against chagas disease
Carolina Macedo Koeller, Norton Heise
Enzyme Research, 2011
Acidocalcisomes as calcium- and polyphosphate-storage compartments during embryogenesis of the insect rhodnius prolixus stahl
Isabela Ramos, Fabio Gomes, Carolina M. Koeller, Katsuharu Saito, Norton Heise, Hatisaburo Masuda, Roberto Docampo, Wanderley de Souza, Ednildo A. Machado, Kildare Miranda
Plos One, 2011
Na+-ATPase and protein kinase C are targets to 1-O-hexadecylphosphocoline (miltefosine) in Trypanosoma cruzi
Victor Barbosa Saraiva, Mira Wengert, Elaine Gomes-Quintana, Norton Heise, Celso Caruso-Neves
Archives of Biochemistry and Biophysics, 2009
Molecular analysis of a UDP-GlcNAc: Polypeptide α-N-acetylglucosaminyltransferase implicated in the initiation of mucin-type O-glycosylation in Trypanosoma cruzi
Norton Heise, Divyendu Singh, Hanke van der Wel, Slim O Sassi, Jennifer M Johnson, Christa L Feasley, Carolina M Koeller, Jose O Previato, Lucia Mendonça-Previato, Christopher M West
Glycobiology, 2009
The toxic effects of piperine against Trypanosoma cruzi: Ultrastructural alterations and reversible blockage of cytokinesis in epimastigote forms
Leonardo Freire-de-Lima, Tatiana Santana Ribeiro, Gustavo Miranda Rocha, Bruno Alves Brandão, Alexandre Romeiro, Lucia Mendonça-Previato, José Osvaldo Previato, Marco Edilson Freire de Lima, Técia Maria Ulisses de Carvalho, Norton Heise
Parasitology Research, 2008
Chemical structure of major glycoconjugates from parasites
Lucia Mendonca-Previato, Adriane Todeschini, Norton Heise, Orlando Agrellos, Wagner Dias, Jose Previato
Current Organic Chemistry, 2008
Cloning and characterization of the phosphoglucomutase of Trypanosoma cruzi and functional complementation of a Saccharomyces cerevisiae PGM null mutant
Luciana L. Penha, Lucia Mendonça-Previato, Jose O. Previato, Julio Scharfstein, Norton Heise, Ana Paula C. de A. Lima
Glycobiology, 2005
Protozoan parasite-specific carbohydrate structures
Lucia Mendonça-Previato, Adriane Regina Todeschini, Norton Heise, Jose Osvaldo Previato
Current Opinion in Structural Biology, 2005
Characterization of the inositol phosphorylceramide synthase activity from Trypanosoma cruzi
Juliana M. FIGUEIREDO, Wagner B. DIAS, Lucia MENDONÇA-PREVIATO, José O. PREVIATO, Norton HEISE
Biochemical Journal, 2005
Nitrogen-fixing bacterium Burkholderia brasiliensis produces a novel yersiniose A - Containing O-polysaccharide
K. A. Mattos
Glycobiology, 2005
B cell response during infection with the MAT a and MAT alpha mating types of Cryptococcus neoformans
Adila Regina T. Santos Rodrigues, Norton Heise, José Osvaldo Previato, Lucia Mendonça-Previato, Ligia M.T. Peçanha
Microbes and Infection, 2005
Toxic effects of natural piperine and its derivatives on epimastigotes and amastigotes of Trypanosoma cruzi
Tatiana Santana Ribeiro, Leonardo Freire-de-Lima, José Osvaldo Previato, Lucia Mendonça-Previato, Norton Heise, Marco Edilson Freire de Lima
Bioorganic and Medicinal Chemistry Letters, 2004
Glycoinositolphospholipid from Trypanosoma cruzi: Structure, Biosynthesis and Immunobiology
J PREVIATO, R WAIT, C JONES, G DOSREIS, A TODESCHINI, N HEISE, L MENDONCAPREVIATO
Advances in Parasitology, 2003
Proinflammatory and cytotoxic effects of hexadecylphosphocholine (miltefosine) against drug-resistant strains of Trypanosoma cruzi
Victor B. Saraiva, Daniel Gibaldi, José O. Previato, Lucia Mendonça-Previato, Marcelo T. Bozza, Célio G. Freire-de-Lima, Norton Heise
Antimicrobial Agents and Chemotherapy, 2002
Molecular analysis of a novel family of complex glycoinositolphosphoryl ceramides from Cryptococcus neoformans: Structural differences between encapsulated and acapsular yeast forms
N. Heise, A. L.S. Gutierrez, K. A. Mattos, C. Jones, R. Wait, J. O. Previato, L. Mendonca-Previato
Glycobiology, 2002
Characterization of novel structures of mannosylinositolphosphoryl-ceramides from the yeast forms of sporothrix schenckii
Carla V. Loureiro y Penha, Adriane R. Todeschini, Leila M. Lopes‐Bezerra, Robin Wait, Christopher Jones, Katherine A. Mattos, Norton Heise, Lucia Mendonça‐Previato, Jose O. Previato
European Journal of Biochemistry, 2001
Structure of an acidic exopolysaccharide produced by the diazotrophic endophytic bacterium Burkholderia brasiliensis
Katherine A. Mattos, Christopher Jones, Norton Heise, José O. Previato, Lúcia Mendonça‐Previato
European Journal of Biochemistry, 2001
An unexpected "4 + 2" [N3S]/[NS] rhenium(IV) complex formed upon cleavage of a Re(V) imido bond
Xiaoyuan Chen, Frank J. Femia, John W. Babich, Jon Zubieta
Inorganica Chimica Acta, 2000
BC63 - Chemical synthesis of the dihydroxyacetonephosphate pathway substrates for studies of the ether-lipid biosynthesis in Trypanosoma cruzi
Memorias do Instituto Oswaldo Cruz, 2000
Ether-lipid (alkyl-phospholipid) metabolism and the mechanism of action of ether-lipid analogues in Leishmania
Henning Lux, Norton Heise, Thomas Klenner, David Hart, Fred R. Opperdoes
Molecular and Biochemical Parasitology, 2000
Localisation of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the mitochondrial matrix of Trypanosoma brucei procyclics
Norton Heise, Fred R. Opperdoes
Zeitschrift Fur Naturforschung Section C Journal of Biosciences, 2000
Purification, localisation and characterisation of glucose-6-phosphate dehydrogenase of Trypanosoma brucei
Norton Heise, Fred R. Opperdoes
Molecular and Biochemical Parasitology, 1999
The dihydroxyacetonephosphate pathway for biosynthesis of ether lipids in Leishmania mexicana promastigotes
Norton Heise, Fred R Opperdoes
Molecular and Biochemical Parasitology, 1997
Identification of complete precursors for the glycosylphosphatidylinositol protein anchors of Trypanosoma cruzi
Norton Heise, Jayne Raper, Laurence U. Buxbaum, Tereza M.S. Peranovich, Maria Lucia Cardoso de Almeida
Journal of Biological Chemistry, 1996
Paracoccidioides brasiliensis Expresses Both Glycosylphosphatidylinositol-Anchored Proteins and a Potent Phospholipase C
Norton Heise, Luiz R Travassos, Maria Lucia Cardoso de Almeida
Experimental Mycology, 1995
Characterization of the lipid moiety of the glycosylphosphatidylinositol anchor of Trypanosoma cruzi 1G7-antigen
Norton Heise, M.Lucia Cardoso de Almeida, Michael A.J. Ferguson
Molecular and Biochemical Parasitology, 1995
Rabbit knee-joint meniscal proteoglycans
Biochemistry and Molecular Biology International, 1994
Characterization of a phospholipase C-resistant inositol containing glycolipid from Trypanosoma cruzi.
Brazilian Journal of Medical and Biological Research Revista Brasileira De Pesquisas Medicas E Biologicas Sociedade Brasileira De Biofisica Et Al, 1994
Proteins anchored via glycosylphosphatidylinositol and solubilizing phospholipases in Trypanosoma cruzi
Biological Research, 1993
Age-related changes in glycosaminoglycan distribution in different anatomical sites on the surface of knee-joint articular cartilage in young rabbits
Norton Heise, Olga M.S. Toledo
Annals of Anatomy, 1993
Mucin-like glycoproteins linked to the membrane by glycosylphosphatidylinositol anchor are the major acceptors of sialic acid in a reaction catalyzed by trans-sialidase in metacyclic forms of Trypanosoma cruzi
Sergio Schenkman, Michael A.J. Ferguson, Norton Heise, Maria Lucia Cardoso de Almeida, Renato A. Mortara, Nobuko Yoshida
Molecular and Biochemical Parasitology, 1993
Glycosaminoglycans in the synovial fluids of patients with juvenile rheumatoid arthritis
Clinical and Experimental Rheumatology, 1991

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Scopus Publications