The structural organization of the human aldehyde reductase gene, AKR1A1, and mapping to chromosome 1p33→p32

Fujii, Junichi; Hamaoka, Rieko; Matsumoto, Akira; Fujii, Tomoko; Yamaguchi, Yuji; Egashira, Masayuki; Miyoshi, Osamu; Niikawa, Norio; Taniguchi, Nobuyuki

doi:10.1159/000015265

Cited by 7 publications

(6 citation statements)

References 11 publications

(14 reference statements)

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“…The enzyme aldehyde reductase is encoded by the AKR1A1 gene [47, 48]. It is involved in the reduction of biogenic and xenobiotic aldehydes and is present in most tissues [49, 50].…”

Section: Metabolism Of Carbonylsmentioning

confidence: 99%

Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls

Singh

Kapoor

Bhatnagar

2015

Chemico-Biological Interactions

125

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Extensive research has shown that increased production of reactive oxygen species (ROS) results in tissue injury under a variety of pathological conditions and chronic degenerative diseases. While ROS are highly reactive and can incite significant injury, polyunsaturated lipids in membranes and lipoproteins are their main targets. ROS-triggered lipid peroxidation reactions generate a range of reactive carbonyl species (RCS), and these RCS spread and amplify ROS-related injury. Several RCS generated in oxidizing lipids, such as 4-hydroxy trans-2-nonenal (HNE), 4-oxo-2-(E)-nonenal (ONE), acrolein, malondialdehyde (MDA) and phospholipid aldehydes have been shown to be produced under conditions of oxidative stress and contribute to tissue injury and dysfunction by depleting glutathione and other reductants leading to the modification of proteins, lipids, and DNA. To prevent tissue injury, these RCS are metabolized by several oxidoreductases, including members of the aldo-keto reductase (AKR) superfamily, aldehyde dehydrogenases (ALDHs), and alcohol dehydrogenases (ADHs). Metabolism via these enzymes results in RCS inactivation and detoxification, although under some conditions, it can also lead to the generation of signaling molecules that trigger adaptive responses. Metabolic transformation and detoxification of RCS by oxidoreductases prevent indiscriminate ROS toxicity, while at the same time, preserving ROS signaling. A better understanding of RCS metabolism by oxidoreductases could lead to the development of novel therapeutic interventions to decrease oxidative injury in several disease states and to enhance resistance to ROS-induced toxicity.

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“…The enzyme aldehyde reductase is encoded by the AKR1A1 gene [47, 48]. It is involved in the reduction of biogenic and xenobiotic aldehydes and is present in most tissues [49, 50].…”

Section: Metabolism Of Carbonylsmentioning

confidence: 99%

Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls

Singh

Kapoor

Bhatnagar

2015

Chemico-Biological Interactions

125

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“…Excessive production of ROS perturbs the redox balance and lead to oxidative stress [7]. To overcome cellular oxidative stress, cells possess different antioxidant enzyme systems including superoxide dismutase, catalase, and glutathione systems [8,9]. Glutathione depletion has been found as a common feature of apoptotic cell death triggered by a wide variety of stimuli [10].…”

Section: Introductionmentioning

confidence: 99%

Lysosomal membrane permeabilization causes oxidative stress and ferritin induction in macrophages

et al. 2011

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Edited by Vladimir SkulachevKeywords: Apoptosis Ferritin Lysosomes MnSOD GSH Oxidative stress a b s t r a c t Moderate lysosomal membrane permeabilization (LMP) is an important inducer of apoptosis. Macrophages are professional scavengers and are rich in hydrolytic enzymes and iron. In the present study, we found that LMP by lysosomotropic detergent MSDH resulted in early up-regulation of lysosomal cathepsins, oxidative stress and ferritin up-regulation, and cell death. Lysosomotropic base NH 4 Cl reduced the ferritin induction and oxidative stress in apoptotic cells induced by MSDH. Cysteine cathepsin inhibitors significantly protected cell death and oxidative stress, but had less effect on ferritin induction. We conclude that oxidative stress induced by lysosomal rupture causes ferritin induction with concomitant mitochondrial damage, which are the potential target for prevention of cellular oxidative stress and cell death induced by typical lysosomotropic substances in different disorders.

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“…AKR1A1 was one of the rst AKRs to be discovered [41]. The AKR1A1 genome, located on chromosome 1p33-p32, contains eight exons and is 16 kb in length [41].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive clinical analysis of AKR1 expression profiles in the diagnosis of human colorectal cancer

Duan

et al. 2023

Preprint

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Background: CRC has a high mortality rate, and early detection is essential to reducing the CRC-related mortality rate. Screening is inefficient for diagnosis based on the low detection rate, length of time consumed, and poor compliance, so more sensitive and effective diagnostic markers are needed to improve diagnostic efficiency. Aldo-keto reductase family-1 enzymes (AKR1s) play a crucial role in the NADPH-dependent reduction of various carbonyl substrates (aldehyde, ketone), and their expression is closely linked with the progression and invasion of malignant cancers. However, the expression patterns of AKR1 family members in colorectal cancer (CRC) and their unique roles in the diagnosis of CRC have not been explored. Here, the mRNA and protein expression levels of 10 AKR1s and their unique roles in diagnosis in CRC were clarified. Methods: We examined the transcription, methylation and survival data of AKR1s in CRC patients from the Oncomine, Gene Expression Profile Interactive Analysis (GEPIA), Kaplan‒Meier Plotter, cBioPortal and Illumina databases. Then, the mRNA and protein expression levels in CRC tissues were assessed by qRT‒PCR and Western blotting. Results: This study showed that the transcript and protein expression levels of AKR1B1, AKR1B10, AKR1B15, AKR1C1, and AKR1C2 were decreased in CRC tissues compared with adjacentnormal tissues. In contrast, the expression levels of AKR1A1 and AKR1C4 were increased in CRC tissues compared with normal tissues. These expression trends were mostly consistent with those for the Oncomine, GEPIA, TCGA and cBioPortal database analyses, and AKR1B1, AKR1C1 and AKR1C2 were significantly downregulated based in their high CpG methylation levels. The qRT–PCR analysis of AKR1 expression in CRC patients with different clinicopathological characteristics showed that the AKR1A1 expression level was related to invasion depth, and the AKR1C2 expression level was significantly related to TNM stage and distant metastasis. The GEPIA results showed that the malignant degree increased with the increase of AKR1C1, AKR1C2 and AKR1C4 concentration, but the opposite was true for AKR1A1, and ROC curve analysis showed that a low level of AKR1B10 and a high level of AKR1C4 had high diagnostic efficacy in the diagnosis of CRC, with sensitivity values of 71.8% and 70.4% and specificity values of 93.0% and 79.6%, respectively. Conclusion: In summary, the study revealed that AKR1A1 and AKR1C4 have good diagnostic value for CRC and could become potential tumour biomarkers. AKR1B1, AKR1B10 and AKR1B15 may be favourable prognostic indicators.

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The structural organization of the human aldehyde reductase gene, AKR1A1, and mapping to chromosome 1p33→p32

Cited by 7 publications

References 11 publications

Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls

Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls

Lysosomal membrane permeabilization causes oxidative stress and ferritin induction in macrophages

Comprehensive clinical analysis of AKR1 expression profiles in the diagnosis of human colorectal cancer

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