When liver cells undergo malignant transformation, certain genes cease being expressed. We have studied the structure of one such gene, whose protein product we have designated hepatic protein 22 (hp22), which is not expressed in the two Morris hepatomas studied. We have prepared a chimeric clone of pBR322 containing cDNA sequences complementary to mRNA coding for this protein. By using this cloned cDNA, we have examined changes in expression of this gene and changes in the restriction pattern of the DNA isolated from normal liver and these hepatomas. In both hepatomas, studies using the isoschizomeric pair of restriction enzymes Msp I and Hpa II have indicated hypermethylation of a cytosine residue within or proximal to the hp22 gene. Other differences in the restriction pattern between normal liver and hepatoma DNA were also detected with EcoRI and Ava I. Thus, in the nontranscribed form of this gene, the DNA has undergone covalent modification, distinguishing these two hepatomas from each other and from normal liver.
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http://dx.doi.org/10.1073/pnas.78.2.834 | DOI Listing |
World J Gastroenterol
January 2025
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.
Background: Liver injury manifesting as hepatic enzyme abnormalities, has been occasionally identified to be a feature of primary or secondary Addison's disease, an uncommon endocrine disease characterized by adrenal insufficiency. There have been no more than 30 reported cases of liver injury explicitly attributed to Addison's disease. Liver injury resulting from adrenal insufficiency due to glucocorticoid withdrawal is exceptionally rarer.
View Article and Find Full Text PDFCancer Metab
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Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany.
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Pediatr Nephrol
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Novo Nordisk A/S, Lexington, MA, USA.
Background: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder with dysregulated glyoxylate metabolism in the liver. Oxalate over-production leads to renal stones, progressive kidney damage and renal failure, with potentially life-threatening systemic oxalosis. Nedosiran is a synthetic RNA interference therapy, designed to reduce hepatic lactate dehydrogenase (LDH) to decrease oxalate burden in PH.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USA.
Liver x receptor alpha (LXRα) functions as an intracellular cholesterol sensor that regulates lipid metabolism at the transcriptional level in response to the direct binding of cholesterol derivatives. We have generated mice with a mutation in LXRα that reduces activity in response to endogenous cholesterol derived LXR ligands while still allowing transcriptional activation by synthetic agonists. The mutant LXRα functions as a dominant negative that shuts down cholesterol sensing.
View Article and Find Full Text PDFJ Control Release
January 2025
Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Republic of Singapore. Electronic address:
mRNA-loaded lipid nanoparticles (mRNA-LNPs) hold great potential for disease treatment and prevention. LNPs are normally made from four lipids including ionizable lipid, helper lipid, cholesterol, and PEGylated lipid (PEG-lipid). Although PEG-lipid has the lowest content, it plays a crucial role in the effective delivery of mRNA-LNPs.
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