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Inhibition of cytosolic class 3 aldehyde dehydrogenase by antisense oligonucleotides in rat hepatoma cells
- Source :
- Chemico-Biological Interactions. :219-225
- Publication Year :
- 2001
- Publisher :
- Elsevier BV, 2001.
-
Abstract
- Aldehyde dehydrogenases (ALDHs) are a superfamily of several isoenzymes widely expressed in bacteria, yeast, plant and animals. Three major classes of ALDHs have been traditionally identified, classes 1, 2 and 3. Both exogenous and endogenous aldehydes, including aldehydes derived from lipid peroxidation, are oxidized by the ALDH superfamily. Several changes in ALDH isoenzyme expression take place in hepatoma cells, in particular cytosolic class 3 ALDH (ALDH3), not expressed in normal hepatocytes, appears and increases with the degree of deviation. It has been demonstrated that cytosolic ALDH3 is important in determining the resistance of tumor cells to antitumor drugs, such as cyclophosphamide. Moreover, hepatoma-associated ALDH3 seems to be important in metabolizing aldehydes derived from lipid peroxidation, and in particular the cytostatic aldehyde 4-hydroxynonenal (4-HNE). We demonstrated previously that restoring endogenous lipid peroxidation in hepatoma cells by enriching them with arachidonic acid causes a decrease of mRNA, protein and enzyme activity of ALDH3 and that this decrease reduces cell growth and/or causes cell death, depending on basal class 3 ALDH activity. To confirm the correlation between inhibition of class 3 ALDH and reduction of cell proliferation, we exposed hepatoma cells to antisense oligonucleotides (ODNs) against ALDH3. In JM2 hepatoma cell line, with high ALDH3 activity, the exposure to antisense ODNs significantly decreases mRNA and enzyme activity (90%). At the same time, cell growth was reduced by about 70%. The results confirm that in hepatoma cells ALDH3 expression is closely related with cell growth, and that its inhibition is important in reducing the proliferation of hepatoma cells overexpressing ALDH3.
- Subjects :
- Aldehyde dehydrogenase
Antisense oligonucleotides
Cell proliferation
Hepatoma cells
Lipid peroxidation
Programmed cell death
Cell division
Gene Expression
Endogeny
Biology
Toxicology
Isozyme
chemistry.chemical_compound
Cytosol
Liver Neoplasms, Experimental
Tumor Cells, Cultured
Animals
RNA, Messenger
RNA, Neoplasm
Enzyme Inhibitors
Cell growth
General Medicine
Aldehyde Dehydrogenase
Oligonucleotides, Antisense
Molecular biology
Rats
Biochemistry
chemistry
biology.protein
Cell Division
Subjects
Details
- ISSN :
- 00092797
- Database :
- OpenAIRE
- Journal :
- Chemico-Biological Interactions
- Accession number :
- edsair.doi.dedup.....ed8ae7492f8f994bb6af1f39a7c4291f