Ability of different hepatoma cells to metabolize 4‐hydroxynonenal

Canuto, Rosa Angela; Muzio, Giuliana; Maggiora, Marina; Poli, Giuseppe; Biasi, Fiorella; Dianzani, Mario U.; Ferro, Margherita; Bassi, Anna Maria; Penco, Susanna; Marinari, Umberto M.

doi:10.1002/cbf.290110202

Cited by 17 publications

(11 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, as we reported elsewhere [5], 4hydroxynonenal is metabolized preferentially by glutathione Stransferase and alcohol dehydrogenase located in the cytosol. In hepatoma cell lines, there are changes in the pattern of metabolism in correlation with the degree of deviation : class 3 cytosolic ALDH assumes importance in 4-hydroxynonenal metabolism [5,16], whereas class 2 mitochondrial ALDH, glutathione Stransferase and alcohol dehydrogenase decrease their metabolic capability [9]. There is an increase in class 3 ALDH activity, as described above, and a decrease in the activity of other enzymes.…”

Section: Introductionmentioning

confidence: 91%

“…The ALDH family is widely expressed in tissues and subcellular components, but with some differences regarding the individual isoenzymes. For example, in liver class 2 mitochondrial ALDH is well expressed, whereas class 3 cytosolic ALDH is not present [8][9][10]. In the cornea and lens, there are high levels of class 3 cytosolic ALDH [11,12], the biological role of which could be important in the oxidation of peroxidic aldehydes, in UV-B photoprotection, and in preventing oxidative damage by free radical species [11].…”

Section: Introductionmentioning

confidence: 99%

“…Compared with normal hepatocytes, cytosolic class 3 ALDH appears in rat hepatoma cells, whereas the levels of class 2 ALDH are significantly decreased [5,8,9,13]. The activity of class 3 ALDH increases with the degree of deviation in hepatoma cell lines, as also occurs in chemically induced hepatocarcinogenesis in i o [5,[14][15][16].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Increase in class 2 aldehyde dehydrogenase expression by arachidonic acid in rat hepatoma cells

et al. 2001

View full text Add to dashboard Cite

Aldehyde dehydrogenase (ALDH) is a family of several isoenzymes important in cell defence against both exogenous and endogenous aldehydes. Compared with normal hepatocytes, in rat hepatoma cells the following changes in the expression of ALDH occur: cytosolic class 3 ALDH expression appears and mitochondrial class 2 ALDH decreases. In parallel with these changes, a decrease in the polyunsaturated fatty acid content in membrane phospholipids occurs. In the present study we demonstrated that restoring the levels of arachidonic acid in 7777 and JM2 rat hepatoma cell lines to those seen in hepatocytes decreases hepatoma cell growth, and increases class 2 ALDH activity. This latter effect appears to be due to an increased gene transcription of class 2 ALDH. To account for this increase, we examined whether peroxisome-proliferator-activated receptors (PPARs) or lipid peroxidation were involved. We demonstrated a stimulation of PPAR expression, which is different in the two hepatoma cell lines: in the 7777 cell line, there was an increase in PPAR alpha expression, whereas PPAR gamma expression increased in JM2 cells. We also found increased lipid peroxidation, but this increase became evident at a later stage when class 2 ALDH expression had already increased. In conclusion, arachidonic acid added to the culture medium of hepatoma cell lines is able to partially restore the normal phenotype of class 2 ALDH, in addition to a decrease in cell growth.

show abstract

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increase in class 2 aldehyde dehydrogenase expression by arachidonic acid in rat hepatoma cells

et al. 2001

View full text Add to dashboard Cite

show abstract

“…HNE metabolism was studied in hepatocytes [ 293 , 300 , 302 , 306 ], hepatoma cells [ 307 , 308 , 309 , 310 ], ascites tumor cells [ 264 ], mucosal cells [ 297 ], synovial fibroblasts [ 295 ], thymocytes [ 294 ], vascular smooth muscle cells [ 311 ] and also in organs such as heart [ 264 , 312 ] and kidney [ 296 , 298 ]. The rapid HNE degradation found and the intracellular metabolism implicate that HNE can rapidly enter cells.…”

Section: Metabolism Of Hnementioning

confidence: 99%

4-Hydroxy-nonenal—A Bioactive Lipid Peroxidation Product

Siems²,

et al. 2015

View full text Add to dashboard Cite

This review on recent research advances of the lipid peroxidation product 4-hydroxy-nonenal (HNE) has four major topics: I. the formation of HNE in various organs and tissues, II. the diverse biochemical reactions with Michael adduct formation as the most prominent one, III. the endogenous targets of HNE, primarily peptides and proteins (here the mechanisms of covalent adduct formation are described and the (patho-) physiological consequences discussed), and IV. the metabolism of HNE leading to a great number of degradation products, some of which are excreted in urine and may serve as non-invasive biomarkers of oxidative stress.

show abstract

“…Knowing that the Erk-1/2 signaling pathway is associated with cell proliferation and survival (Cobb et al, 1994;Chen et al, 2001), the association between pro-oxidant-induced growth inhibition and the inhibition of this pathway becomes clear. Although some investigations suggest that 4-HNE activates Erk-1/2 phosphorylation in cultures of various cell lines (Iles et al, 2003;Iles and Liu, 2005), recent evidence shows that cell lines profoundly differ from their primary counterparts with respect to 4-HNE metabolism and sensitivity (Canuto et al, 1993(Canuto et al, , 1994. These observations emphasize the justification for using primary cells when investigating the effects of 4-HNE on normal, constitutive cellular functions in particular signal transduction pathways.…”

mentioning

confidence: 99%

4-Hydroxy-2-nonenal Adduction of Extracellular Signal-Regulated Kinase (Erk) and the Inhibition of Hepatocyte Erk-Est–Like Protein-1-Activating Protein-1 Signal Transduction

Sampey¹,

Carbone²,

Doorn³

et al. 2006

Mol Pharmacol

View full text Add to dashboard Cite

4-Hydroxy-2-nonenal (4-HNE) is a major lipid peroxidation (LPO) product formed during oxidative stress. 4-HNE is highly reactive toward cellular nucleophiles and is implicated in the evolution of numerous pathologies associated with oxidative stress and LPO. Recent evidence suggests that chronic prooxidant exposure results in the loss of extracellular signalregulated kinase (Erk)-1/2 phosphorylation in vivo, a signaling pathway associated with cellular proliferation, survival, and homeostasis. Immunodetection and molecular analysis were used in this study to evaluate the hypothesis that 4-HNE modification of Erk-1/2 inhibits constitutive Erk-Est-like protein (Elk)-1-activating protein (AP)-1 signaling. Primary rat hepatocytes treated with subcytotoxic, pathologically relevant concentrations of 4-HNE demonstrated a concentration-dependent loss of constitutive Erk-1/2 phosphorylation, activity, and nuclear localization. These findings were consistent with iron-induced intracellular LPO, which also resulted in a concentration-dependent decrease in hepatocyte Erk-1/2 phosphorylation and activity. 4-HNE and iron-induced inhibition of Erk-1/2 was inversely correlated with the accumulation of 4-HNE-Erk-1/2 monomer adducts. 4-HNE treatment of hepatocytes decreased nuclear total and phosphorylated Erk-1/2, Elk-1, and AP-1 phosphorylation as well as cFos and cJun activities. The cytosolic modification of unphosphorylated Erk-1/2 was evaluated in vitro using molar ratios of inactive Erk-2 to 4-HNE consistent with increasing oxidative stress in vivo. Liquid chromatography combined with tandem mass spectrometry confirmed monomer adduct formation and identified the major adduct species at the histidine 178 residue within the kinase phosphorylation lip. These novel results show that the formation of 4-HNE-Erk-1/2 monomer-adducts results in the inhibition of Erk-Elk-AP-1 signaling in hepatocytes and implicates the His 178 residue with the mechanism of inhibition.Oxidative stress and the subsequent formation of reactive oxygen species (ROS) have been correlated with a number of disease states, in animal models and in the clinical setting. Recent evidence suggests that the major lipid peroxidation product 4-hydroxy-2-nonenal (4-HNE) is associated with several hepatic disease states, including alcoholic liver disease, hepatic iron overload, hepatitis C, and primary biliary cirrhosis (Paradis et al., 1997a,b). Although the temporal relationship between 4-HNE and oxidative stress has long since been established, the protein-specific effects of pro-oxidantinduced 4-HNE production on hepatic dysfunction have only recently begun to be revealed.The diverse cellular effects of lipid aldehydes result from their diffusible nature and rapid reactivity (Benedetti et al., 1979). 4-HNE has been shown to modify cysteine (Cys), his-

show abstract

Ability of different hepatoma cells to metabolize 4‐hydroxynonenal

Cited by 17 publications

References 27 publications

Increase in class 2 aldehyde dehydrogenase expression by arachidonic acid in rat hepatoma cells

Increase in class 2 aldehyde dehydrogenase expression by arachidonic acid in rat hepatoma cells

4-Hydroxy-nonenal—A Bioactive Lipid Peroxidation Product

4-Hydroxy-2-nonenal Adduction of Extracellular Signal-Regulated Kinase (Erk) and the Inhibition of Hepatocyte Erk-Est–Like Protein-1-Activating Protein-1 Signal Transduction

Contact Info

Product

Resources

About