Article
Chemistry, Medicinal
Hua-Lin Zhou, Alfred Hausladen, Puneet Anand, Malligarjunan Rajavel, Colin T. Stomberski, Rongli Zhang, Richard T. Premont, William J. Greenlee, Focco van den Akker, Jonathan S. Stamler
Summary: Acute kidney injury (AKI) is a serious condition with high morbidity and mortality, and there are currently no drugs available for treatment. However, the deletion of S-nitrosocoenzyme A reductase 2 (SCoR2; AKR1A1) has been found to protect mice against AKI through metabolic reprogramming, suggesting that SCoR2 could be a potential drug target.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Kohji Yamamoto, Satoshi Endo
Summary: This study characterized a new AKR, AKR2E8, in silkworms, which showed similar properties to human AKR1B1 and AKR1B10 and was found to play a major role in aldehyde detoxification in the midgut. The findings may aid in developing pest control methods for lepidopterans, such as silkworms, that damage crops.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Francesc Xavier Ruiz, Xavier Pares, Jaume Farres
Summary: Human aldo-keto reductase 1B10 (AKR1B10) is overexpressed in many cancer types and has been identified as an interesting drug target. Differences in inhibitor binding between AKR1B10 and aldose reductase (AR) have been observed, highlighting specific features that a selective AKR1B10 inhibitor should possess.
Article
Plant Sciences
Romina Minen, Jaina A. Bhayani, Matias D. Hartman, Antonela E. Cereijo, Yuanzhang Zheng, Miguel A. Ballicora, Alberto A. Iglesias, Dali Liu, Carlos M. Figueroa
Summary: This study presents the crystal structures of key enzymes involved in sugar alcohol synthesis in celery and peach. The findings highlight the relationship between the structure and function of these enzymes, providing important insights into the process of sugar alcohol synthesis in plants.
PLANT AND CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kohji Yamamoto, Satoshi Endo
Summary: We studied the effects of green leaf volatiles emitted by plants on insects, focusing on AKR2E9, a potential insect-resistance gene in silkworms. We found that AKR2E9 might regulate the detoxification of toxic aldehydes in the midgut and antennae of silkworms.
ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Shiori Takano, Tatsuki Fukami, Hiroyuki Ichida, Kohei Suzuki, Masataka Nakano, Miki Nakajima
Summary: The study investigated the effects of single-nucleotide polymorphisms (SNPs) in the AKR1C3 gene on the reductase activities of clinical drugs. The C145Y variant of AKR1C3 showed significantly lower reductase activities for acetohexamide, doxorubicin, and loxoprofen. Furthermore, individuals with the heterozygous genotype of the g.55101G>A SNP tended to exhibit lower reductase activities for these drugs compared to individuals with the homozygous wild-type genotype.
DRUG METABOLISM AND DISPOSITION
(2023)
Review
Biochemistry & Molecular Biology
Burak Mugdat Karan, Karis Little, Josy Augustine, Alan W. Stitt, Tim M. Curtis
Summary: Diabetic retinopathy (DR) is a complication of diabetes mellitus that can cause vision loss and blindness. This review article explores the impact of oxidative stress, lipid-derived aldehydes, and advanced lipoxidation end products (ALEs) on the progression of DR. It also highlights the importance of aldehyde metabolism in the retina, particularly the role of aldehyde dehydrogenase (ALDH) and aldo-keto reductase (AKR) enzymes. The review discusses potential therapeutic strategies, such as gene therapy and pharmacological compounds, that can enhance the expression and activity of ALDH and AKR enzymes to protect the retina and preserve vision in diabetic patients.
Article
Biochemistry & Molecular Biology
Mubashir Aziz, Syeda Abida Ejaz, Nissren Tamam, Farhan Siddique
Summary: This study identifies theobromine and theophylline as strong inhibitors of AKR1B1 and AKR1B10, with potential anti-cancer activity against various tumor proteins. The findings contribute to the development and repurposing of AKR1B1/AKR1B10 inhibitors for the treatment of colon cancer and associated malignancies.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Plant Sciences
Alka Jangra, Siddhant Chaturvedi, Sonia Sihag, Garima Sharma, Siddharth Tiwari, Vinod Chhokar
Summary: This study discovered a plant aldo-ketoreductase isolated from Aloe vera leaves, revealing its catalytic potential in polyketide biosynthesis and providing new insights for tailored biosynthesis of plant polyketides for therapeutic purposes.
Article
Biochemistry & Molecular Biology
Wenhao Qu, Yajun Bai, Tai-Ping Fan, Xiaohui Zheng, Yujie Cai
Summary: This study found that Lactobacillus reuteri DSM20016 has multiple aldo-keto reductases (AKRs) that can use NADPH as a coenzyme to convert various aldehydes to alcohols under slightly acidic conditions, giving Lactobacillus reuteri a complex aroma.
PROCESS BIOCHEMISTRY
(2022)
Article
Food Science & Technology
Yogita Lugani, Munish Puri, Balwinder Singh Sooch
Summary: Xylose reductase is an industrially important food enzyme that plays a crucial role in converting xylose into xylitol, with diverse applications in various industries.
EUROPEAN FOOD RESEARCH AND TECHNOLOGY
(2021)
Article
Oncology
Tiangen Wu, Yang Ke, Haoran Tang, Chen Liao, Jinze Li, Lin Wang
Summary: Fidarestat shows efficacy in treating a variety of tumors, with its role in hepatocellular carcinoma (HCC) explored in a mouse model. It inhibits tumor growth and metastasis, increases NK cell activity, and downregulates AKR1B10 expression to promote NK cell glycolysis against HCC cells.
MOLECULAR THERAPY-ONCOLYTICS
(2021)
Article
Biochemistry & Molecular Biology
Ronghua Chen, Siwei Wang, Yue Sun, Haiqing Li, Shuqing Wan, Fei Lin, Hanhong Xu
Summary: Genes that participate in the degradation or isolation of glyphosate in plants have the potential to confer herbicide tolerance and low glyphosate residue in crops. The aldo-keto reductase (AKR4) gene in Echinochloa colona (EcAKR4) has been identified as a naturally evolved glyphosate-metabolism enzyme. This study compared the glyphosate-degradation ability of AKR4 proteins from maize, soybean, and rice, revealing that ZmAKR4 had the highest activity and OsAKR4-1 and OsAKR4-2 exhibited the highest activity among the AKR4 family in rice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Syeda Abida Ejaz, Mubashir Aziz, Aftab Ahmed, Saqer S. S. Alotaibi, Sarah M. M. Albogami, Farhan Siddique, Gaber El-Saber Batiha
Summary: The aim of this research is to investigate the quantum geometric properties and chemical reactivity of atropine. Computational methods were used to determine the stable geometry of atropine and calculate various molecular parameters. Molecular docking analysis showed that atropine has greater inhibitory action against AKR1B1 than AKR1B10. Simulation data and ADMET characteristics were used to predict the drug likeness of atropine. This research suggests that atropine has potential as an inhibitor of AKR1B1 for the treatment of colon cancer associated with AKR1B1 expression.
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
(2023)
Article
Agronomy
Feng-Yan Zhou, Heping Han, Yun-Jing Han, Alex Nyporko, Qin Yu, Hugh J. J. Beckie, Stephen B. B. Powles
Summary: The expression of AKR genes (LrAKR4C10 and LrAKR1) in glyphosate-resistant populations of Lolium rigidum from Western Australia is induced by glyphosate and 2,4-D, resulting in enhanced glyphosate metabolism and moderate resistance to glyphosate.
PEST MANAGEMENT SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Satoshi Endo, Mina Kawai, Manami Hoshi, Jin Segawa, Mei Fujita, Takuo Matsukawa, Naohiro Fujimoto, Toshiyuki Matsunaga, Akira Ikari
Summary: Prostate cancer usually has a good prognosis, but long-term hormone therapy may lead to castration-resistant prostate cancer (CRPC). Cabazitaxel is used in CRPC treatment, but its tolerance is a major issue. In this study, it was found that Nrf2 signaling is homeostatically activated in cabazitaxel-resistant cells, and inhibiting Nrf2 signaling can enhance sensitivity to cabazitaxel.
JOURNAL OF BIOCHEMISTRY
(2021)
Article
Biotechnology & Applied Microbiology
Zeljka Trumbic, Jerko Hrabar, Nikola Palevich, Vincenzo Carbone, Ivona Mladineo
Summary: Parasitism is a successful life strategy that has evolved multiple times, with accidental infections providing opportunities for lateral host switches. However, when directed towards phylogenetically distant hosts like humans, certain parasites may fail to mature due to host immunity. The study on Anisakis larvae migrating through rats and fish reveals differences in gene expression patterns, shedding light on the evolution of nematode virulence and potential drug therapy targets.
Article
Biochemistry & Molecular Biology
Ayaka Ito, Haruka Nasako, Risa Akizuki, Yui Takashina, Hiroaki Eguchi, Toshiyuki Matsunaga, Yuta Yoshino, Satoshi Endo, Akira Ikari
Summary: CLDN2 induces chemoresistance in spheroid cells by inhibiting glucose transport and activating the Nrf2 signal pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Kyoko Kamase, Maki Taguchi, Akira Ikari, Satoshi Endo, Toshiyuki Matsunaga
Summary: This study found that 9,10-phenanthrenequinone (9,10-PQ) in diesel exhaust particle (DEP) is toxic to human vascular cells, inducing cell apoptosis and dysfunction of the blood-brain barrier through a ROS-dependent mechanism. Additionally, the down-regulation of the tight junctional protein CLDN5 may contribute to the dysfunction, while the formation of nitric oxide (NO) and peroxynitrite also play a role in this process.
Review
Biochemistry & Molecular Biology
Satoshi Endo, Toshiyuki Matsunaga, Toru Nishinaka
Summary: AKR1B10 is highly expressed in epithelial cells of the stomach and intestine, but down-regulated in gastrointestinal cancers and inflammatory bowel diseases. It is lowly expressed in other tissues, but upregulated in cancers, non-alcoholic fatty liver disease, and several skin diseases. The enzyme's expression is elevated in cancer cells resistant to clinical anti-cancer drugs.
Correction
Chemistry, Medicinal
Yudai Kudo, Satoshi Endo, Mei Fujita, Atsumi Ota, Yuji O. Kamatari, Yoshimasa Tanaka, Takeshi Ishikawa, Hayato Ikeda, Takuya Okada, Naoki Toyooka, Naohiro Fujimoto, Toshiyuki Matsunaga, Akira Ikari
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yudai Kudo, Satoshi Endo, Mei Fujita, Atsumi Ota, Yuji O. Kamatari, Yoshimasa Tanaka, Takeshi Ishikawa, Hayato Ikeda, Takuya Okada, Naoki Toyooka, Naohiro Fujimoto, Toshiyuki Matsunaga, Akira Ikari
Summary: This study discovered inhibitors of Atg4B, a key enzyme in autophagosome formation, and evaluated their potential as therapeutics for prostate cancer. Compound 17 showed the most potent Atg4B inhibitory activity and enhanced the anticancer activity of anti-CRPC drugs. Through structural optimization, compound 21f was developed as a competitive inhibitor with strong inhibitory activity against Atg4B.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Hiroaki Eguchi, Riho Kimura, Haruka Matsunaga, Toshiyuki Matsunaga, Yuta Yoshino, Satoshi Endo, Akira Ikari
Summary: This study found that fisetin can enhance the toxicity of anticancer drugs in A549 lung adenocarcinoma spheroids by reducing CLDN2 expression, potentially through inhibiting the PI3K/Akt signaling pathway and affecting hypoxia levels in the tumor microenvironment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Sofia Khanum, Vincenzo Carbone, Sandeep K. Gupta, Juliana Yeung, Dairu Shu, Tania Wilson, Natalie A. Parlane, Eric Altermann, Silvia M. Estein, Peter H. Janssen, D. Neil Wedlock, Axel Heiser
Summary: In this study, B- and T-cell epitopes of a model antigen from a methanogen were mapped using a combination of in silico predictions and experimental validation. It was found that the epitopes identified by in silico predictions did not match those determined empirically.
SCIENTIFIC REPORTS
(2022)
Article
Microbiology
Bishwa P. Subedi, Linley R. Schofield, Vincenzo Carbone, Maximilian Wolf, William F. Martin, Ron S. Ronimus, Andrew J. Sutherland-Smith
Summary: Archaea have diverse cell wall types, including pseudomurein in some methanogens. Crystal structures of methanogen pseudomurein peptide ligases (pMurE) were determined, revealing their structural similarity to bacterial MurE peptide ligases. The presence of pMurE ligases in Methanobacteriales and Methanopyrales supports the evolutionary relationship between archaeal pseudomurein and bacterial peptidoglycan cell walls.
Article
Biochemistry & Molecular Biology
Hiroaki Eguchi, Riho Kimura, Saki Onuma, Ayaka Ito, Yaqing Yu, Yuta Yoshino, Toshiyuki Matsunaga, Satoshi Endo, Akira Ikari
Summary: Claudin-2 is abnormally expressed in lung adenocarcinoma, and caffeine and theobromine can decrease its protein level, while enhancing the toxicity of doxorubicin in A549 cells. This effect may be achieved by accelerating lysosomal degradation of CLDN2 and reducing Nrf2 expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yudai Kudo, Satoshi Endo, Masatoshi Tanio, Tomofumi Saka, Rin Himura, Naohito Abe, Mitsumi Takeda, Eiji Yamaguchi, Yuta Yoshino, Yuki Arai, Hirohito Kashiwagi, Masayoshi Oyama, Akichika Itoh, Masaki Shiota, Naohiro Fujimoto, Akira Ikari
Summary: This study reveals the important roles of adrenal-derived 11-oxygenated androgens and DHRS11 in the progression of prostate cancer. It also identifies a novel DHRS11 inhibitor, KC-A, which suppresses androgen signaling and enhances the anticancer activity of a CRPC drug. These findings suggest that KC-A may be a potential candidate for the prevention and treatment of CRPC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Toshiyuki Matsunaga, Misato Horinouchi, Haruhi Saito, Aki Hisamatsu, Kazuhiro Iguchi, Yuta Yoshino, Satoshi Endo, Akira Ikari
Summary: Paclitaxel (PTX) is commonly used for breast cancer chemotherapy, but continuous treatment causes hyposensitivity. This study found that acquiring chemoresistance leads to up-regulation of aldo-keto reductase (AKR) 1C3. Inhibiting AKR1C3 and reducing its expression increased MCF7 cell sensitivity to PTX, while overexpression of AKR1C3 decreased sensitivity. The resistant cells were less sensitive to cytotoxic aldehydes derived from ROS-mediated lipid peroxidation and showed reduced levels of these aldehydes during PTX treatment. AKR1C3 inhibition mitigated this reduction, suggesting its role in the development of PTX resistance. The resistance also promoted abnormal expression of ABC transporter ABCB1, and combined treatment with AKR1C3 and ABCB1 inhibitors overcame PTX resistance and cross-resistance to docetaxel.
JOURNAL OF BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Satoshi Endo, Yoshifumi Morikawa, Toshiyuki Matsunaga, Akira Hara, Masaki Takasu
Summary: A porcine gene, LOC100622246, encodes carbonyl reductase [NADPH] 1 (pCBR-N1), whose function remains unknown. Previously, three porcine carbonyl reductases, carbonyl reductase 1 (pCBR1), 3 alpha/ss-hydroxysteroid dehydrogenase (p3 alpha/ss-HSD) and prostaglandine-9-keto reductase (pPG-9-KR), were purified from different pig tissues. The relationship between pCBR-N1 and these three enzymes is still unknown. This study compared the properties of pCBR-N1 and pCBR1 and found that pCBR-N1 is identical to p3 alpha/ss-HSD and pPG-9-KR. pCBR-N1 is a glutathione-activated carbonyl reductase that functions in the metabolism of endogenous and xenobiotic carbonyl compounds.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Vincenzo Carbone, Kerri Reilly, Carrie Sang, Linley R. Schofield, Ron S. Ronimus, William J. Kelly, Graeme T. Attwood, Nikola Palevich
Summary: Pectin is an important polysaccharide in plants that can be degraded by pectin methylesterase (PME) to release methanol. Butyrivibrio bacteria play a key role in pectin degradation and methanol production in the rumen. Studying the crystal structure and catalytic mechanism of PMEs has potential applications in reducing methane emissions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)