Modulation of the heme oxygenase HO-1 expression by hyperosmolarity and betaine in primary rat hepatocytes. 2001

M R Lordnejad, and F Schliess, and M Wettstein, and D Häussinger
Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-Universität, Düsseldorf, Germany.

The influence of hyperosmotic shrinkage and the osmolyte betaine on heme oxygenase HO-1 expression was studied in cultured rat hepatocytes. Hyperosmolarity transiently suppressed HO-1 induction in response to hemin or medium addition at the levels of mRNA and protein expression. Pretreatment of the cells with betaine largely restored induction of both HO-1 mRNA and protein under hyperosmotic conditions. Exposure of HO-1-expressing hepatocytes to cycloheximide unraveled a hyperosmotic acceleration of HO-1 degradation which was counteracted by betaine and the proteolysis inhibitor MG-132. The HO-1 mRNA stability remained unaffected by hyperosmolarity and betaine as shown by application of the transcription inhibitor actinomycin D. The data suggest a modulation of HO-1 expression by hyperosmolarity and betaine at the transcriptional level and at the level of proteasomal degradation. Hyperosmotic suppression of HO-1 expression was accompanied by a moderate but significant loss of hepatocyte viability, which was prevented by betaine. The hyperosmotic impairment of hepatocyte viability was insensitive to betaine in presence of the heme oxygenase inhibitor zinc protoporphyrin IX. However, treatment of the hepatocytes with bilirubin or 8-Br-cGMP improved hepatocyte viability under hyperosmotic conditions to the control niveau. Thus, stabilizing HO-1 expression may contribute to hepatocyte protection against hyperosmotic stress by organic osmolytes.

UI MeSH Term Description Entries
D008082 Lipotropic Agents Endogenous factors or drugs that increase the transport and metabolism of LIPIDS including the synthesis of LIPOPROTEINS by the LIVER and their uptake by extrahepatic tissues. Lipotropic Factors,Lipocaic,Lipotropic Drugs,Lipotropics,Agents, Lipotropic,Drugs, Lipotropic,Factors, Lipotropic
D008297 Male Males
D009994 Osmolar Concentration The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent. Ionic Strength,Osmolality,Osmolarity,Concentration, Osmolar,Concentrations, Osmolar,Ionic Strengths,Osmolalities,Osmolar Concentrations,Osmolarities,Strength, Ionic,Strengths, Ionic
D010447 Peptide Hydrolases Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES. Peptidase,Peptidases,Peptide Hydrolase,Protease,Proteases,Proteinase,Proteinases,Proteolytic Enzyme,Proteolytic Enzymes,Esteroproteases,Enzyme, Proteolytic,Hydrolase, Peptide
D006419 Heme Oxygenase (Decyclizing) A mixed function oxidase enzyme which during hemoglobin catabolism catalyzes the degradation of heme to ferrous iron, carbon monoxide and biliverdin in the presence of molecular oxygen and reduced NADPH. The enzyme is induced by metals, particularly cobalt. Haem Oxygenase,Heme Oxygenase,Oxygenase, Haem,Oxygenase, Heme
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
D001622 Betaine A naturally occurring compound that has been of interest for its role in osmoregulation. As a drug, betaine hydrochloride has been used as a source of hydrochloric acid in the treatment of hypochlorhydria. Betaine has also been used in the treatment of liver disorders, for hyperkalemia, for homocystinuria, and for gastrointestinal disturbances. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1341) Lycine,Oxyneurine,Acidin-Pepsin,Betaine Hydrochloride,C.B.B.,Citrate de Bétaïne Beaufour,Citrate de Bétaïne UPSA,Cystadane,Glycine Betaine,Hepastyl,Novobetaine,Scorbo-bétaïne,Stea-16,Acidin Pepsin,AcidinPepsin,Betaine, Glycine,Hydrochloride, Betaine,Scorbo bétaïne,Scorbobétaïne,Stea 16,Stea16
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
D015971 Gene Expression Regulation, Enzymologic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis. Enzymologic Gene Expression Regulation,Regulation of Gene Expression, Enzymologic,Regulation, Gene Expression, Enzymologic
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats

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