Modulation of hepatic microsomal triglyceride transfer protein (MTP) induced by S-nitroso-N-acetylcysteine in ob/ob mice. 2007

Claudia P M S Oliveira, and Venâncio A F Alves, and Vicência M R Lima, and José Tadeu Stefano, and Victor Debbas, and Sandra Valéria Sá, and Alda Wakamatsu, and Maria Lúcia Corrêa-Giannella, and Evandro Sobroza de Mello, and Sofia Havaki, and Dina G Tiniakos, and Evangelos Marinos, and Marcelo G de Oliveira, and Daniel Giannella-Neto, and Francisco R Laurindo, and Stephen Caldwell, and Flair J Carrilho
Department of Gastroenterology, University of São Paulo School of Medicine, Brazil. cpm@usp.br

We evaluated the effects of a potent NO donor, S-nitroso-N-acetylcysteine (SNAC), on microsomal triglyceride transfer protein (MTP) expression in ob/ob mice. NAFLD was induced in male ob/ob mice using a methionine-choline deficient diet (MCD) concomitantly with oral SNAC fed solution (n=5) or vehicle (control; n=5) by gavage daily for 4 weeks. Livers were collected for histology and for assessing MTP by RT-qPCR, Western blot, immunohistochemistry and immunogold electron microscopy analyses. Histological analysis showed diffuse macro and microvesicular steatosis, moderate hepatocellular ballooning and moderate inflammatory infiltrate in ob/ob mice fed the MCD diet. With SNAC, mice showed a marked reduction in liver steatosis (p<0.01), in parenchymal inflammation (p=0.02) and in MTP protein immunoexpression in zone III (p=0.05). Moreover, SNAC caused reduction of MTP protein in Western blot analysis (p<0.05). In contrast, MTP mRNA content was significantly higher (p<0.05) in mice receiving SNAC. Immuno-electron microscopy showed MTP localized in the rough endoplasmic reticulum of hepatocytes in both treated and untreated groups. However with SNAC treatment, MTP was also observed surrounding fat globules. Histological improvement mediated by a nitric oxide donor is associated with significantly altered expression and distribution of MTP in this animal model of fatty liver disease. Further studies are in progress to examine possible mechanisms and to develop SNAC as a possible therapy for human fatty liver disease.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008820 Mice, Obese Mutant mice exhibiting a marked obesity coupled with overeating, hyperglycemia, hyperinsulinemia, marked insulin resistance, and infertility when in a homozygous state. They may be inbred or hybrid. Hyperglycemic Mice,Obese Mice,Mouse, Hyperglycemic,Mouse, Obese,Hyperglycemic Mouse,Mice, Hyperglycemic,Obese Mouse
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D005234 Fatty Liver Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS. Liver Steatosis,Steatohepatitis,Steatosis of Liver,Visceral Steatosis,Liver Steatoses,Liver, Fatty,Steatohepatitides,Steatoses, Liver,Steatoses, Visceral,Steatosis, Liver,Steatosis, Visceral,Visceral Steatoses
D000111 Acetylcysteine The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. Mercapturic Acid,Acemuc,Acetabs,Acetylcystein AL,Acetylcystein Atid,Acetylcystein Heumann,Acetylcystein Trom,Acetylcysteine Hydrochloride,Acetylcysteine Sodium,Acetylcysteine Zinc,Acetylcysteine, (D)-Isomer,Acetylcysteine, (DL)-Isomer,Acetylcysteine, Monoammonium Salt,Acetylcysteine, Monosodium Salt,Acetylin,Acetyst,Acétylcystéine GNR,Airbron,Alveolex,Azubronchin,Bisolvon NAC,Bromuc,Broncho-Fips,Broncholysin,Broncoclar,Codotussyl,Cystamucil,Dampo Mucopect,Eurespiran,Exomuc,Fabrol,Fluimucil,Fluprowit,Frekatuss,Genac,Hoestil,Ilube,Jenacystein,Jenapharm,Lantamed,Larylin NAC,Lindocetyl,M-Pectil,Muciteran,Muco Sanigen,Mucomyst,Mucosil,Mucosol,Mucosolvin,N-Acetyl-L-cysteine,N-Acetylcysteine,NAC AL,NAC Zambon,Optipect Hustengetränk,Siccoral,Siran,Solmucol,acebraus,durabronchal,mentopin Acetylcystein,Acetylcystein, mentopin,Acid, Mercapturic,Broncho Fips,BronchoFips,Hustengetränk, Optipect,Hydrochloride, Acetylcysteine,M Pectil,MPectil,Monoammonium Salt Acetylcysteine,Monosodium Salt Acetylcysteine,Mucopect, Dampo,N Acetyl L cysteine,N Acetylcysteine,NAC, Bisolvon,Sanigen, Muco,Sodium, Acetylcysteine,Zambon, NAC,Zinc, Acetylcysteine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D020133 Reverse Transcriptase Polymerase Chain Reaction A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols. Polymerase Chain Reaction, Reverse Transcriptase,Reverse Transcriptase PCR,PCR, Reverse Transcriptase,Transcriptase PCR, Reverse

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