scholarly journals S-adenosylmethionine in Liver Health, Injury, and Cancer

2012 ◽  
Vol 92 (4) ◽  
pp. 1515-1542 ◽  
Author(s):  
Shelly C. Lu ◽  
José M. Mato
Keyword(s):  
Liver Diseases ◽  
Mammalian Cells ◽  
Human Liver ◽  
Normal Liver ◽  
Experimental Models ◽  
Chemopreventive Agent ◽  
Liver Health ◽  
Liver Transaminases ◽  
Extrahepatic Tissues ◽  
Cholestasis Of Pregnancy

S-adenosylmethionine (AdoMet, also known as SAM and SAMe) is the principal biological methyl donor synthesized in all mammalian cells but most abundantly in the liver. Biosynthesis of AdoMet requires the enzyme methionine adenosyltransferase (MAT). In mammals, two genes, MAT1A that is largely expressed by normal liver and MAT2A that is expressed by all extrahepatic tissues, encode MAT. Patients with chronic liver disease have reduced MAT activity and AdoMet levels. Mice lacking Mat1a have reduced hepatic AdoMet levels and develop oxidative stress, steatohepatitis, and hepatocellular carcinoma (HCC). In these mice, several signaling pathways are abnormal that can contribute to HCC formation. However, injury and HCC also occur if hepatic AdoMet level is excessive chronically. This can result from inactive mutation of the enzyme glycine N-methyltransferase (GNMT). Children with GNMT mutation have elevated liver transaminases, and Gnmt knockout mice develop liver injury, fibrosis, and HCC. Thus a normal hepatic AdoMet level is necessary to maintain liver health and prevent injury and HCC. AdoMet is effective in cholestasis of pregnancy, and its role in other human liver diseases remains to be better defined. In experimental models, it is effective as a chemopreventive agent in HCC and perhaps other forms of cancer as well.

scholarly journals Equilibrative Nucleoside Transporters Mediate the Import of Nicotinamide Riboside and Nicotinic Acid Riboside into Human Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1391
Author(s):  
Andrey Kropotov ◽  
Veronika Kulikova ◽  
Kirill Nerinovski ◽  
Alexander Yakimov ◽  
Maria Svetlova ◽  
...  
Keyword(s):  
Nicotinic Acid ◽  
Mammalian Cells ◽  
Experimental Models ◽  
The Body ◽  
Nucleoside Transporters ◽  
Hek293 Cells ◽  
Nucleoside Transporter ◽  
Vitamin B3 ◽  
Animal Cells ◽  
Nicotinamide Riboside

Nicotinamide riboside (NR), a new form of vitamin B3, is an effective precursor of nicotinamide adenine dinucleotide (NAD+) in human and animal cells. The introduction of NR into the body effectively increases the level of intracellular NAD+ and thereby restores physiological functions that are weakened or lost in experimental models of aging and various pathologies. Despite the active use of NR in applied biomedicine, the mechanism of its transport into mammalian cells is currently not understood. In this study, we used overexpression of proteins in HEK293 cells, and metabolite detection by NMR, to show that extracellular NR can be imported into cells by members of the equilibrative nucleoside transporter (ENT) family ENT1, ENT2, and ENT4. After being imported into cells, NR is readily metabolized resulting in Nam generation. Moreover, the same ENT-dependent mechanism can be used to import the deamidated form of NR, nicotinic acid riboside (NAR). However, NAR uptake into HEK293 cells required the stimulation of its active utilization in the cytosol such as phosphorylation by NR kinase. On the other hand, we did not detect any NR uptake mediated by the concentrative nucleoside transporters (CNT) CNT1, CNT2, or CNT3, while overexpression of CNT3, but not CNT1 or CNT2, moderately stimulated NAR utilization by HEK293 cells.

Detection of a Microsomal Antigen and Its Antibody in Human Liver Diseases

1979 ◽  
Vol 59 (4) ◽  
pp. 459-464 ◽  
Author(s):  
E. Penner ◽  
S.O. Emejuaiwe ◽  
F. Milgrom
Keyword(s):  
Liver Diseases ◽  
Human Liver ◽  
Microsomal Antigen

Cellular retinol-binding protein-1 (CRBP-1), a useful adjunct to pathologists to identify hepatic stellate cells (HSC) in human liver diseases

2003 ◽  
Vol 38 ◽  
pp. 54
Author(s):  
S. Lepreux ◽  
A. Desmouliere ◽  
J. Rosenbaum ◽  
G. Gabbiani ◽  
C. Balabaud ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Liver Diseases ◽  
Human Liver ◽  
Binding Protein ◽  
Stellate Cells ◽  
Retinol Binding Protein ◽  
Cellular Retinol Binding Protein

scholarly journals Biology of the immunomodulatory molecule HLA-G in human liver diseases

2015 ◽  
Vol 62 (6) ◽  
pp. 1430-1437 ◽  
Author(s):  
Laurence Amiot ◽  
Nicolas Vu ◽  
Michel Samson
Keyword(s):  
Liver Diseases ◽  
Human Liver

scholarly journals Identification of Catalposide Metabolites in Human Liver and Intestinal Preparations and Characterization of the Relevant Sulfotransferase, UDP-glucuronosyltransferase, and Carboxylesterase Enzymes

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 355 ◽  
Author(s):  
Deok-Kyu Hwang ◽  
Ju-Hyun Kim ◽  
Yongho Shin ◽  
Won-Gu Choi ◽  
Sunjoo Kim ◽  
...  
Keyword(s):  
Human Liver ◽  
Individual Variability ◽  
Hydroxybenzoic Acid ◽  
Catalpa Ovata ◽  
Anti Oxidant ◽  
Extrahepatic Tissues ◽  
Udp Glucuronosyltransferase ◽  
Hydrolysis Of

Catalposide, an active component of Veronica species such as Catalpa ovata and Pseudolysimachion lingifolium, exhibits anti-inflammatory, antinociceptic, anti-oxidant, hepatoprotective, and cytostatic activities. We characterized the in vitro metabolic pathways of catalposide to predict its pharmacokinetics. Catalposide was metabolized to catalposide sulfate (M1), 4-hydroxybenzoic acid (M2), 4-hydroxybenzoic acid glucuronide (M3), and catalposide glucuronide (M4) by human hepatocytes, liver S9 fractions, and intestinal microsomes. M1 formation from catalposide was catalyzed by sulfotransferases (SULTs) 1C4, SULT1A1*1, SULT1A1*2, and SULT1E1. Catalposide glucuronidation to M4 was catalyzed by gastrointestine-specific UDP-glucuronosyltransferases (UGTs) 1A8 and UGT1A10; M4 was not detected after incubation of catalposide with human liver preparations. Hydrolysis of catalposide to M2 was catalyzed by carboxylesterases (CESs) 1 and 2, and M2 was further metabolized to M3 by UGT1A6 and UGT1A9 enzymes. Catalposide was also metabolized in extrahepatic tissues; genetic polymorphisms of the carboxylesterase (CES), UDP-glucuronosyltransferase (UGT), and sulfotransferase (SULT) enzymes responsible for catalposide metabolism may cause inter-individual variability in terms of catalposide pharmacokinetics.

Human liver carboxylesterase 1 outperforms alpha-fetoprotein as biomarker to discriminate hepatocellular carcinoma from other liver diseases in Korean patients

2013 ◽  
Vol 133 (2) ◽  
pp. 408-415 ◽  
Author(s):  
Keun Na ◽  
Seul-Ki Jeong ◽  
Min Jung Lee ◽  
Sang Yun Cho ◽  
Sun A Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Diseases ◽  
Human Liver ◽  
Alpha Fetoprotein ◽  
Korean Patients ◽  
Carboxylesterase 1

scholarly journals Genome-wide transcriptome analysis identifies novel gene signatures implicated in human chronic liver disease

2013 ◽  
Vol 305 (5) ◽  
pp. G364-G374 ◽  
Author(s):  
Rana L. Smalling ◽  
Don A. Delker ◽  
Yuxia Zhang ◽  
Natalia Nieto ◽  
Michael S. Mcguiness ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hepatitis C ◽  
Liver Function ◽  
Chronic Liver Disease ◽  
Nuclear Receptor ◽  
Liver Diseases ◽  
Human Liver ◽  
Chronic Liver ◽  
Rna Seq ◽  
Gene Signatures

The molecular mechanisms behind human liver disease progression to cirrhosis remain elusive. Nuclear receptor small heterodimer partner (SHP/ Nr0b2) is a hepatic tumor suppressor and a critical regulator of liver function. SHP expression is diminished in human cirrhotic livers, suggesting a regulatory role in human liver diseases. The goal of this study was to identify novel SHP-regulated genes that are involved in the development and progression of chronic liver disease. To achieve this, we conducted the first comprehensive RNA sequencing (RNA-seq) analysis of Shp−/− mice, compared the results with human hepatitis C cirrhosis RNA-seq and nonalcoholic steatohepatitis (NASH) microarray datasets, and verified novel results in human liver biospecimens. This approach revealed new gene signatures associated with chronic liver disease and regulated by SHP. Several genes were selected for validation of physiological relevance based on their marked upregulation, novelty with regard to liver function, and involvement in gene pathways related to liver disease. These genes include peptidoglycan recognition protein 2, dual specific phosphatase-4, tetraspanin 4, thrombospondin 1, and SPARC-related modular calcium binding protein-2, which were validated by qPCR analysis of 126 human liver specimens, including steatosis, fibrosis, and NASH, alcohol and hepatitis C cirrhosis, and in mouse models of liver inflammation and injury. This RNA-seq analysis identifies new genes that are regulated by the nuclear receptor SHP and implicated in the molecular pathogenesis of human chronic liver diseases. The results provide valuable transcriptome information for characterizing mechanisms of these diseases.

Effects of chronic liver diseases on mitochondrial DNA transcription and replication in human liver

Life Sciences ◽  
1999 ◽  
Vol 65 (5) ◽  
pp. 557-563 ◽  
Author(s):  
Katsuhiro Kotake ◽  
Toshiaki Nonami ◽  
Tsuyoshi Kurokawa ◽  
Akimasa Nakao ◽  
Taro Murakami ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Liver Diseases ◽  
Human Liver ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Dna Transcription ◽  
Transcription And Replication
Sign in / Sign up

Export Citation Format

Share Document