Elevation of aldose reductase gene expression in rat primary hepatoma and hepatoma cell lines: Implication in detoxification of cytotoxic aldehydes

Takahashi, M.; Fujii, Junichi; Miyoshi, Eiji; Hoshi, Ayumu; Taniguchi, Naoyuki

doi:10.1002/ijc.2910620617

Cited by 72 publications

(61 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because AR exhibits broad specificity for both hydrophilic and hydrophobic aldehydes, it has been suggested that this enzyme may detoxify compounds with an aldehyde moiety and confer resistance to cells against cytotoxicity of toxic compounds. 37 It is noteworthy that the mouse FR-1 mRNA showing the highest sequence homology with the novel HARP gene is high in the newborn but not in the adult liver, and is induced by fibroblast growth factor. 33 Furthermore, recent reports showing the increased expression of AR gene in induced rat hepatoma are in accordance with our finding of HARP mRNA in all tested human HCC samples.…”

Section: Discussionmentioning

confidence: 99%

“…33 Furthermore, recent reports showing the increased expression of AR gene in induced rat hepatoma are in accordance with our finding of HARP mRNA in all tested human HCC samples. [36][37][38] Carbohydrate metabolism is known to play an important role in the liver during embryonic development. Re-expression of AR could be assumed to be a consequence of unbalanced biological functions during tumor development.…”

Section: Discussionmentioning

confidence: 99%

“…[33][34][35] Recent reports showing the increased expression of AR gene in induced rat hepatoma are in accordance with our findings in human HCC. [36][37][38] 30 cycles , followed by an extension at 68°C for 7 minutes on a GeneAmp PCR system 9600 (Perkin-Elmer Corp., Norwalk, CT), each PCR reaction was stopped by the addition of Stop Solution (Amersham). Samples were heated at 94°C for 2 minutes and analyzed on a denaturing 4.5% polyacrylamide gel using a GenomyxLR DNA Sequencer (Genomyx, Foster City, CA).…”

mentioning

confidence: 99%

See 2 more Smart Citations

New member of aldose reductase family proteins overexpressed in human hepatocellular carcinoma

et al. 1998

View full text Add to dashboard Cite

The multistep process of liver carcinogenesis involves various genetic and phenotypic alterations. To identify genes whose expression is increased during hepatocarcinogenesis, differential-display polymerase chain reaction (DD-PCR) was used to examine differences in the mRNA composition of hepatocellular carcinoma (HCC) versus normal liver (nontumor) tissues. This approach identified 67 cDNAs that were preferentially expressed in HCC tissue. When these cDNAs were analyzed by reverse-Northern analysis, five were reproducibly expressed at high levels in HCC. Interestingly, Northern blot analysis revealed that one of the genes showed significantly increased mRNA levels in all five tested tumor samples, while its mRNA level in the nontumor samples was minimal. BLAST analysis revealed that this gene has high sequence identity with the genes from aldo-keto reductase family of proteins including the mouse fibroblast growth factor-induced gene (FR-1) (80% identity), mouse vas deferens protein (MVDP) (76%), and human aldose reductase (AR) (62%). Expression of this novel AR-related protein in all five tested HCCs suggests that this protein may play an important role in liver carcinogenesis. (HEPATOLOGY 1998;27:943-950.) Hepatocellular carcinoma (HCC) is a multiformed and aggressive tumor, and is the fourth-most common tumor in the world today. In Asia and Africa, HCC is one of the major causes of cancer death because of its high frequency and poor prognosis. 1 The risk factors associated with HCC include chronic infections with hepatitis B virus or hepatitis C virus and prolonged dietary consumption of aflatoxins, alcohol, or iron overload. More recently, it has been shown that the relative risk for development of HCC is increased synergistically among individuals exposed to both aflatoxins and hepatitis B virus. 2 The incidence of HCC is expected to increase significantly in the next decade, mainly because of the increasing number of patients infected with hepatitis C virus.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

New member of aldose reductase family proteins overexpressed in human hepatocellular carcinoma

et al. 1998

View full text Add to dashboard Cite

show abstract

“…AR as a tumor-associated variant 40 was detected in 60% of HCC. This is comparable with the results of Cao et al 24 ; they found that in the Asian population, 54% of investigated HCC expressed ARL-1 mRNA and 29% expressed AR mRNA.…”

Section: Discussionmentioning

confidence: 99%

Detection and identification of tumor-associated protein variants in human hepatocellular carcinomas

et al. 2004

View full text Add to dashboard Cite

The proteomic approach is a valuable tool to detect and identify proteins that are associated with cancer. In previous investigations on experimentally induced rat hepatomas, we detected aldose reductase-like protein (ARLP) as a highly significant marker protein. Our present study was intended to look for the presence of similar tumor-associated marker proteins on human hepatocellular carcinomas (HCC). We found several novel tumorassociated protein variants that represent members of the aldo-keto reductase (AKR) superfamily. Human aldose reductase-like protein-1 (hARLP-1) was the most prominent tumorassociated AKR member detected in HCC by 2-dimensional electrophoresis (2-DE) and identified by mass spectrometric fingerprinting. The enzyme was found in 4 distinct forms H uman hepatocellular carcinoma (HCC) ranks fifth in worldwide cancer incidence and is an important component of public health. Many HCC risk factors are known, including hepatitis B or C (HBV or HCV) infection, ingestion of aflatoxin-contaminated food, and alcohol. 1,2 The development of HCC is associated with multiple changes at the messenger RNA (mRNA) and/or protein level, some of them serving as tumor markers, e.g., ␣-fetoprotein, 3 or, less specifically, cyclin D1 or the proliferating cell nuclear antigen. 4 Misprogramming of genetic information in cancer is reflected by quantitative and/or qualitative protein alterations. These protein alterations might represent tumor markers that are useful in the diagnosis of human tumors and may also help the understanding of mechanisms of tumor induction and development. Proteome analysis of liver proteins and HCC were predominantly performed using either chemically induced hepatomas in animals (predominantly the rat 5-10 ) or human HCC cell lines, such as HepG2 and Huh7 cells, 11 BEL-7404 cells, 12 or HCC-M cells. 2,13,14 Numerous so-called tumor-associated or cancer-related proteins were identified; these provide valuable information for the establishment of HCC protein databases. 2,[11][12][13][14] Comparative analysis of liver tissue and hepatocellular carcinomas might give additional insights into the induction or repression of tumor-associ-

show abstract

“…AKR inducing agents have included ethacrynic acid (9), ethoxyquin (19), 3Ј-methyl-4-dimethyl-aminoazobenzene (20), and N-methyl-N-nitrosourea (21), while spontaneous induction has been observed during the development of hereditary hepatitis leading to hepatocarcinogenesis (6). Hormonal regulation of AKR members has been observed during the estrous cycle (7), in the cell cycle of Leishmania major (22) and due to the effects of basic fibroblast growth factor on astrocytes (8).…”

Section: Resultsmentioning

confidence: 99%

Cloning, Sequencing, and Enzymatic Activity of an Inducible Aldo-Keto Reductase from Chinese Hamster Ovary Cells

Hyndman¹,

Takenoshita²,

Vera³

et al. 1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

Treatment of Chinese hamster ovary (CHO) cells by the aldehyde containing calpain inhibitor I resulted in the induction of a 35-kDa protein that was partially sequenced and shown to be a member of the aldo-keto reductase superfamily (Inoue, S., Sharma, R. C., Schimke, R. T., and Simoni, R. D. (1993) J. Biol. Chem. 268, 5894 -5898). Using rapid amplification of cDNA ends polymerase chain reaction, we have sequenced the cDNA for this protein (CHO reductase). This enzyme is a new member of the aldo-keto reductase superfamily and shows greatest amino acid sequence identity to mouse fibroblast growth factor-regulated protein and mouse vas deferens protein (92 and 80% sequence identity, respectively). The enzyme exhibits about 70% sequence identity with the aldose reductases (ALR2; EC 1.1.1.21) and about 47% with the aldehyde reductases (ALR1; EC 1.1.1.2). Northern analysis showed that it is induced in preference to either ALR1 or ALR2 and RNase protection assays showed gene expression in bladder, testis, jejunum, and ovary in descending order of expression. The cDNA for this inducible reductase was cloned into the pET16b vector and expressed in BL21(DE3) cells. Expressed CHO reductase showed kinetic properties distinct from either ALR1 or ALR2 including the ability to metabolize ketones. This protein joins a growing number of inducible aldo-keto reductases that may play a role in cellular regulation and protection.To characterize the calpain inhibitor I-sensitive protease(s) involved in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, Simoni's group (1) attempted to isolate Chinese hamster ovary (CHO) 1 cells resistant to this peptide aldehyde (N-acetyl-leucyl-leucyl-norleucinal (ALLN)). Instead of inducing a protease, a 35-kDa protein was overexpressed which gave tryptic peptide fragments with a high degree of sequence identity to members of the aldo-keto reductase superfamily. 2 This superfamily is a rapidly growing group of monomeric oxidoreductases containing at least 40 members at present (2). This group includes the aldehyde and aldose reductases, a number of hydroxysteroid dehydrogenases, Shaker channels, and plant chalcone reductases. They are characterized by a TIM-barrel structure (3) and the preferential use of NADPH over NADH. Substrates include aliphatic and aromatic aldehydes, monosaccharides, steroids, prostaglandins, polycyclic aromatic hydrocarbons, and isoflavinoid phytoalexins.Several members of this family have been shown to be induced in response to hormonal or chemical factors. These include fibroblast growth factor-regulated protein (FR-1) (4), mouse vas deferens protein (MVDP) (5), aldose reductase (ALR2) (6 -8), and dihydrodiol dehydrogenase (9). To determine the relationship of this new reductase to the other members of the family we have used RACE PCR to isolate and sequence its mRNA from CHO cells. It shows highest sequence identity to FR-1 and MVDP at 92 and 80%, respectively. FR-1 and MVDP have not been extensively characterized kinetically but CHO reductase showed a greater ...

show abstract

Elevation of aldose reductase gene expression in rat primary hepatoma and hepatoma cell lines: Implication in detoxification of cytotoxic aldehydes

Cited by 72 publications

References 27 publications

New member of aldose reductase family proteins overexpressed in human hepatocellular carcinoma

New member of aldose reductase family proteins overexpressed in human hepatocellular carcinoma

Detection and identification of tumor-associated protein variants in human hepatocellular carcinomas

Cloning, Sequencing, and Enzymatic Activity of an Inducible Aldo-Keto Reductase from Chinese Hamster Ovary Cells

Contact Info

Product

Resources

About