ArticleGastroenterology2006
Hint2, a mitochondrial apoptotic sensitizer down-regulated in hepatocellular carcinoma.
Article in Gastroenterology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 65 citations in OpenAlex.
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- mMolecular cancer · 2019Article
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- Natural Products Containing 'Rare' Organophosphorus Functional Groups.Molecules (Basel, Switzerland) · 2019Review
- Genome-wide differential expression profiling of mRNAs and lncRNAs associated with prolificacy in Hu sheep.Bioscience reports · 2018Article
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- Global deletion of BCATm increases expression of skeletal muscle genes associated with protein turnover.Physiological genomics · 2015Article
- Proteogenomic analysis of human chromosome 9-encoded genes from human samples and lung cancer tissues.Journal of proteome research · 2014Article
- Quantitative proteomics analysis identifies mitochondria as therapeutic targets of multidrug-resistance in ovarian cancer.Theranostics · 2014Article
- Metabolism and pharmacokinetics of the anti-hepatitis C virus nucleotide prodrug GS-6620.Antimicrobial agents and chemotherapy · 2014Article
- Characterization of the effect of the mitochondrial protein Hint2 on intracellular Ca(2+) dynamics.Biophysical journal · 2013Article
- Expression, purification, crystallization and preliminary X-ray crystallographic analysis of human histidine triad nucleotide-binding protein 2 (hHINT2).Acta crystallographica. Section F, Structural biology and crystallization communications · 2013Article
- HINT2 and fatty liver disease: mitochondrial protein hyperacetylation gives a hint?Hepatology (Baltimore, Md.) · 2013Article
- Hits, Fhits and Nits: beyond enzymatic function.Advances in enzyme regulation · 2011Review
- Article
- Tumor suppressor and hepatocellular carcinoma.World journal of gastroenterology · 2008Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 5 countries.
Funding
Abstract
BACKGROUND &
aimsHints, histidine triad nucleotide-binding proteins, are adenosine monophosphate-lysine hydrolases of uncertain biological function. Here we report the characterization of human Hint2.
methodsTissue distribution was determined by real-time quantitative polymerase chain reaction and immunoblotting, cellular localization by immunocytochemistry, and transfection with green fluorescent protein constructs. Enzymatic activities for protein kinase C and adenosine phosphoramidase in the presence of Hint2 were measured. HepG2 cell lines with Hint2 overexpressed or knocked down were established. Apoptosis was assessed by immunoblotting for caspases and by flow cytometry. Tumor growth was measured in SCID mice. Expression in human tumors was investigated by microarrays.
resultsHint2 was predominantly expressed in liver and pancreas. Hint2 was localized in mitochondria. Hint2 hydrolyzed adenosine monophosphate linked to an amino group (AMP-pNA; k(cat):0.0223 s(-1); Km:128 micromol/L). Exposed to apoptotic stress, fewer HepG2 cells overexpressing Hint2 remained viable (32.2 +/- 0.6% vs 57.7 +/- 4.6%), and more cells displayed changes of the mitochondrial membrane potential (87.8 +/- 2.35 vs 49.7 +/- 1.6%) with more cleaved caspases than control cells. The opposite was observed in HepG2 cells with knockdown expression of Hint2. Subcutaneous injection of HepG2 cells overexpressing Hint2 in SCID mice resulted in smaller tumors (0.32 +/- 0.13 g vs 0.85 +/- 0.35 g). Microarray analyses revealed that HINT2 messenger RNA is downregulated in hepatocellular carcinomas (-0.42 +/- 0.58 log2 vs -0.11 +/- 0.28 log2). Low abundance of HINT2 messenger RNA was associated with poor survival.
conclusionHint2 defines a novel class of mitochondrial apoptotic sensitizers down-regulated in hepatocellular carcinoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.