Role of aldo-keto reductases in development of prostate and breast cancer

Jin, Junfei; Krishack, Paulette A.; Cao, Deliang

doi:10.2741/2006

Cited by 38 publications

(31 citation statements)

References 38 publications

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“…AKR1B10 belongs to the aldo-ketoreductase super-gene family consisting of fourteen families and more than 40 members [15,20]. Enhanced expression of aldo-ketoreductases are recognized in several types of tumours, e.g.…”

Section: Discussionmentioning

confidence: 99%

Identification and expression analysis of the aldo–ketoreductase1-B10 gene in primary malignant liver tumours

Heringlake¹,

Hofdmann²,

Fiebeler³

et al. 2010

Journal of Hepatology

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Section: Discussionmentioning

confidence: 99%

Identification and expression analysis of the aldo–ketoreductase1-B10 gene in primary malignant liver tumours

Heringlake¹,

Hofdmann²,

Fiebeler³

et al. 2010

Journal of Hepatology

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“…This might indicate that AKRs are not involved in the maintenance of retinoid homeostasis under normal physiological conditions. However, human AKR1B10 is known to be overexpressed in certain types of cancers, including hepatocellular carcinoma and lung cancer associated with tobacco smoking (56)(57)(58). An upregulation of an enzyme with a potent retinaldehyde reductive activity, such as AKR1B10, might adversely affect the levels of atRA in cancer cells even though AKR1B10 may not be essential for the maintenance of atRA homeostasis under normal conditions.…”

Section: Biosynthesis Of Atra From Retinolmentioning

confidence: 99%

Enzymology of retinoic acid biosynthesis and degradation

Kedishvili

2013

Journal of Lipid Research

170

165

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This article is available online at http://www.jlr.org ( 10 ), and regulation of energy homeostasis ( 11,12 ). atRA exerts its actions by serving as an activating ligand of nuclear atRA receptors [retinoid acid receptor (RAR) ␣ , RAR ␤ , and RAR ␥ ] and peroxisome proliferator-activated receptors (PPAR) ␤ / ␦ , which form heterodimers with retinoid X receptors ( 13,14 ). The actions of the RARs are described in more detail in this thematic series by RochetteEgly and colleagues. The concentration of atRA during embryonic development is tightly controlled in a spatial and temporal manner, and in adult tissues, it is maintained within a very narrow range that is specifi c for each given tissue. If the control mechanisms fail and the concentration of atRA exceeds or falls below the optimal range, tissues and cells undergo pathophysiological changes that in most severe cases can lead to disease. Thus, the maintenance of optimal atRA levels is essential for life. This review focusses on recent fi ndings regarding the mechanisms that control atRA homeostasis, with specifi c emphasis on the enzymes involved in atRA biosynthesis and degradation. All-trans -retinoic acid (atRA) is a highly potent derivative of vitamin A that is required for virtually all essential physiological processes and functions because of its involvement in transcriptional regulation of over 530 different genes ( 1, 2 ). For example, atRA is necessary for differentiation and development of fetal and adult tissues, stem cell differentiation, and apoptosis ( 3-7 ), and for support of reproductive functions ( 8, 9 ), immune response

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“…[17][18][19] In addition to their roles in protection against aflatoxininduced hepatotoxicity and hepatocarcinogenesis, recent evidence also suggests that AKR7A enzymes might also play important roles in Alzheimer's disease 20 and tumorigenesis of prostate, breast, colorectal, and pancreatic cancers. [21][22][23] Furthermore, AKR7A enzymes also have been shown to be involved in the bioactivation and biodetoxification of a number of cytotoxic carbonyl compounds or mutagens. [24][25][26][27] The expression of Akr7a genes, like many other subgroups in the Akr superfamily, 28 are known to be regulated by a variety of intracellular and environmental signals, including ROS, electrophiles, and chemopreventive agents.…”

mentioning

confidence: 99%

Aldo-keto reductase-7A protects liver cells and tissues from acetaminophen-induced oxidative stress and hepatotoxicity

et al. 2011

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Aldo-keto reductase-7A (AKR7A) is an enzyme important for bioactivation and biodetoxification. Previous studies suggested that Akr7a might be transcriptionally regulated by oxidative stress-responsive transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a protein highly responsive to acetaminophen (APAP) or its intermediate metabolite, N-acetyl-p-benzoquinoneimine (NAPQI). This study was, therefore, carried out to investigate whether Akr7a is involved in the protection against APAP-induced oxidative stress and hepatotoxicity. We found that in response to APAP or NAPQI exposure, Akr7a3 mRNA and protein were significantly up-regulated in vitro in human HepG2 and LO2 cells. Similarly, strong induction was observed for Akr7a5 in mouse AML12 hepatocytes exposed to APAP. In vivo in wild-type rats, significant up-regulation of hepatic AKR7A1 protein was observed after administration of APAP. On the other hand, depletion of Nrf2 reduced the expression of Akr7a3, suggesting that Nrf2, indeed, contributes significantly to the induction of Akr7a. Moreover, loss of cell viability in Nrf2-depleted cells was significantly rescued by coexpression of AKR7A3. Furthermore, increased AKR7A3 in HepG2 cells was associated with the up-regulation of oxidative stress-related enzymes to enhance cellular antioxidant defense, which appeared to contribute significantly to protection against APAP-induced toxicity. In a line of transgenic rats overexpressing AKR7A1, increased AKR7A1 stimulated the expression of Nrf2 and other Nrf2-regulated genes, but did not better protect rats from APAP insults. In contrast, depletion of Akr7a5 in vitro in cultured AML12 cells or depletion of Akr7a1 in vivo in rat liver greatly increased APAPinduced hepatotoxicity. Conclusion: AKR7A proteins are significantly up-regulated in response to APAP/NAPQI exposure to contribute significantly to protection against APAP-induced hepatotoxicity. AKR7A mediates this protection, in part, through enhancing hepatocellular antioxidant defense. (HEPATOLOGY 2011;54:1322-1332 A cetaminophen (also called paracetamol, N-acetyl-p-aminophenol, Tylenol V R , and APAP) is a clinically widely used drug with potent analgesic and antipyretic activities. At therapeutic doses, most ingested APAP is metabolized to phenolic glucuronide and sulfate conjugates in the liver by glucuronyltransferases and sulfotransferases and is subsequently excreted in the urine 1 ; however, a small portion is oxidized by cytochrome P450 (CYP450) 2E1 to generate a highly reactive, cytotoxic intermediate: N-acetyl-pAbbreviations: AFAR, aflatoxin aldehyde reductase; AKR, aldo-keto reductase; AKR7A, aldo-keto reductase-7A; ALT, alanine aminotransferase; APAP, acetaminophen; ARE, anti-oxidant response element; AST, aspartate transaminase; Cat, catalase; CMV, cytomegalovirus; CYP450, cytochrome P450; DMSO, dimethylsulfoxide; ERE, estrogen response element; G6PDH, glucose-6-phosphate dehydrogenase; Gpx-1/2, glutathione peroxidase-1/2; GSH, glutathione; GST, glutathione S-transferase; IDH-1,...

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Role of aldo-keto reductases in development of prostate and breast cancer

Cited by 38 publications

References 38 publications

Identification and expression analysis of the aldo–ketoreductase1-B10 gene in primary malignant liver tumours

Identification and expression analysis of the aldo–ketoreductase1-B10 gene in primary malignant liver tumours

Enzymology of retinoic acid biosynthesis and degradation

Aldo-keto reductase-7A protects liver cells and tissues from acetaminophen-induced oxidative stress and hepatotoxicity

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