Review
Medicine, Research & Experimental
Ajinath Kale, Himanshu Sankrityayan, Hans-Joachim Anders, Anil Bhanudas Gaikwad
Summary: Klotho is a novel anti-aging protein expressed at highest levels in the kidney, with its regulation contributing to kidney disease progression. Levels of Klotho decrease during kidney injury and other diseases, but supplementation or overexpression can attenuate kidney disease. Various epigenetic and non-epigenetic mechanisms regulate Klotho expression, with natural products showing potential in this regulation.
Article
Endocrinology & Metabolism
Louis-Charles Desbiens, Aboubacar Sidibe, Roth-Visal Ung, Fabrice Mac-Way
Summary: This study investigated the association between FGF23, alpha-Klotho, and traditional mineral parameters with fractures. The results showed that cFGF23 was linearly associated with fracture incidence, while alpha-Klotho, PTH, and phosphate levels had a U-shaped association.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Biochemistry & Molecular Biology
Khalid Saad Alharbi, Obaid Afzal, Abdulmalik Saleh Alfawaz Altamimi, Waleed Hassan Almalki, Imran Kazmi, Fahad A. Al-Abbasi, Sami Alzarea, Hafiz A. Makeen, Mohammed Albratty
Summary: Aging is a major risk factor for prevalent human illnesses. Senescent cell accumulation and decreased klotho concentrations are associated with aging. Altering the level of klotho/Wnt/β-catenin can slow down aging and the onset of kidney diseases. Drugs that selectively remove senescent cells can extend lifespan.
JOURNAL OF FOOD BIOCHEMISTRY
(2022)
Review
Endocrinology & Metabolism
Pan-Pan Hu, Jing-Fu Bao, Aiqing Li
Summary: The fibroblast growth factor-23-alpha-Klotho axis is closely related to chronic kidney disease and has multiple biological functions beyond bone-mineral metabolism. Dysregulation of this axis has been observed in acute kidney injury, but its exact role in the pathophysiology of acute kidney injury remains largely unknown. It may provide new therapeutic targets for treating acute kidney injury.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2021)
Article
Urology & Nephrology
Xiaowen Chen, Huishi Tan, Jie Xu, Yuan Tian, Qian Yuan, Yangyang Zuo, Qiyan Chen, Xue Hong, Haiyan Fu, Fan Fan Hou, Lili Zhou, Youhua Liu
Summary: The Klotho-derived peptide KP6 mimics the protective effects of Klotho in diabetic kidney disease, alleviating established proteinuria, glomerular hypertrophy, podocyte damage, glomerulosclerosis, and interstitial fibrotic lesions by blocking the Wnt/beta-catenin signaling pathway.
KIDNEY INTERNATIONAL
(2022)
Article
Pharmacology & Pharmacy
Xuying Zhu, Shu Li, Qisheng Lin, Xinghua Shao, Jingkui Wu, Weiming Zhang, Hong Cai, Wenyan Zhou, Na Jiang, Zhen Zhang, Jianxiao Shen, Qin Wang, Zhaohui Ni
Summary: Alpha Klotho protein protects against CI-AKI by inhibiting NLRP3 inflammasome-mediated pyroptosis and promoting autophagy, showing promise as a therapeutic strategy.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Urology & Nephrology
Yuxiuzi Xiao, Zuomiao Xiao
Summary: This study found a negative association between serum Klotho levels and the incidence of kidney stones in diabetic adults in the United States. For every 1 unit increase in ln-transformed Klotho concentration, there was a 28% lower risk of kidney stones.
AMERICAN JOURNAL OF NEPHROLOGY
(2023)
Review
Medicine, General & Internal
Javier Donate-Correa, Ernesto Martin-Nunez, Ainhoa Gonzalez-Luis, Carla M. Ferri, Desiree Luis-Rodriguez, Victor G. Tagua, Carmen Mora-Fernandez, Juan E. Navarro-Gonzalez
Summary: Observational studies have linked the increase in FGF23 levels with the onset of diabetes, suggesting the existence of potential diabetogenic mechanisms originating from chronic supraphysiological levels of FGF23 in CKD and ESRD patients. These mechanisms could involve direct and indirect effects on pancreatic ss cells, as well as the stimulation of pro-inflammatory factors synthesis, potentially mediated by the binding of FGF23 to noncanonical receptor complexes.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Nutrition & Dietetics
Maurice A. G. M. Kroon, Jacqueline K. Berbee, Soumia Majait, Eleonora L. Swart, Olaf van Tellingen, Hanneke W. M. van Laarhoven, E. Marleen Kemper
Summary: The oral intake of curcumin supplements still cannot reach therapeutic plasma levels. Healthcare practitioners need to be skeptical of the claimed beneficial systemic health effects of current curcumin supplement use by their patients.
FRONTIERS IN NUTRITION
(2023)
Article
Nutrition & Dietetics
Qingqing Cai, Shixian Hu, Cancan Qi, Jiawei Yin, Shulan Xu, Fan Fan Hou, An Li
Summary: Adherence to a healthy diet is associated with a reduced risk of kidney dysfunction. This study investigated the role of serum alpha-Klotho, an anti-aging protein, in mediating this relationship. The findings suggest that a healthy diet may promote kidney function by up-regulating serum alpha-Klotho.
Article
Biochemistry & Molecular Biology
Hang-Fei Yu, Yu-Chen Cheng, Cai-Meng Wu, Kun Ran, Bin Wei, You-Kai Xu, Wei-Guang Shan, You-Min Ying, Zha-Jun Zhan
Summary: This study isolated four undescribed regular rosane-type diterpenoids euphominoids M-P and three undescribed rearranged rosane-type diterpenoids euphomilones C-E from the whole plants of Euphorbia milii Des Moul. Their structures were determined by NMR and mass spectroscopy, and their absolute configurations were established by single-crystal X-ray diffraction experiments and comparative analyses of calculated and experimental ECD spectra. One of the compounds exhibited potent inhibitory activity, and it was the first time that rosane-type diterpenoids were reported as β-glucuronidase inhibitors.
Review
Medicine, General & Internal
Meera Gupta, Gabriel Orozco, Madhumati Rao, Roberto Gedaly, Hartmut H. Malluche, Javier A. Neyra
Summary: Cardiovascular disease and mineral bone disorders are major factors affecting patients with chronic kidney disease, both before and after renal transplantation. Hormonal imbalances post-kidney transplant are associated with graft function loss and poor outcomes. Fibroblast growth factor 23 (FGF-23) and alpha-Klotho play crucial roles in the underlying mechanisms of accelerated atherosclerosis, vascular calcification, mineral disorders, and osteodystrophy. Kidney donation also leads to endocrine and metabolic adaptations, but the long-term effects and clinical significance are still unknown.
FRONTIERS IN MEDICINE
(2022)
Article
Urology & Nephrology
Anca Matei, Stefana Catalina Bilha, Daniela Constantinescu, Mariana Pavel-Tanasa, Petru Cianga, Adrian Covic, Dumitru D. Branisteanu
Summary: The study investigated the impact of non-classical bone regulating factors in long-standing kidney transplant recipients compared to the general population. Age, PTH, time on dialysis, and lean mass were identified as main predictors of bone density in KT patients. Adipokine dysregulation and alpha-Klotho's influence on bone outcomes in KT-MBD require further investigation.
JOURNAL OF NEPHROLOGY
(2022)
Review
Veterinary Sciences
Pak-Kan Tang, Rebecca F. Geddes, Rosanne E. Jepson, Jonathan Elliott
Summary: Mineral derangements are common in chronic kidney disease, with the significance of calcium disturbances not fully understood. Understanding the relationships between calcium metabolism and regulating hormones is crucial for predicting potential adverse clinical outcomes in CKD patients.
VETERINARY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Beatriz Martin-Carro, Julia Martin-Virgala, Sara Fernandez-Villabrille, Alejandra Fernandez-Fernandez, Marcos Perez-Basterrechea, Juan F. Navarro-Gonzalez, Javier Donate-Correa, Carmen Mora-Fernandez, Adriana S. Dusso, Natalia Carrillo-Lopez, Sara Panizo, Manuel Naves-Diaz, Jose L. Fernandez-Martin, Jorge B. Cannata-Andia, Cristina Alonso-Montes
Summary: Fibrosis plays a crucial role in the development of diabetic complications and dysfunction in the heart and kidneys. This study investigated the involvement of soluble Klotho, advanced glycation end products/receptor for AGEs, fibrotic Wnt/beta-catenin pathway, and pro-fibrotic pathways in the kidney and heart of diabetic rats. The findings suggested that diabetic rats had elevated levels of urinary sKlotho, AGEs, and sRAGE, and decreased levels of serum sKlotho. Fibrosis and RAGE levels were higher in the heart of diabetic rats compared to controls. The increase in sKlotho and sRAGE excretion may be due to polyuria in diabetic rats.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Masamichi Nagae, Yoshiki Yamaguchi, Naoyuki Taniguchi, Yasuhiko Kizuka
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Chemistry, Analytical
Jun-ichi Furukawa, Hisatoshi Hanamatsu, Takashi Nishikaze, Hiroshi Manya, Nobuaki Miura, Hirokazu Yagi, Ikuko Yokota, Keiko Akasaka-Manya, Tamao Endo, Motoi Kanagawa, Norimasa Iwasaki, Koichi Tanaka
ANALYTICAL CHEMISTRY
(2020)
Review
Biochemistry & Molecular Biology
Naoyuki Taniguchi, Yuki Ohkawa, Kento Maeda, Yoichiro Harada, Masamichi Nagae, Yasuhiko Kizuka, Hideyuki Ihara, Yoshitaka Ikeda
Summary: Cancer-related changes in glycans on cell surface proteins are regulated by glycosyltransferases and related genes, which play key roles in cancer metastasis and invasion. The significance of EMT and N-glycan branching glycosyltransferases needs to be reconsidered for potential therapeutic strategies. Specific glycosyltransferases involved in EMT or MET pathways may be difficult to define due to their roles in intermediate states.
MOLECULAR ASPECTS OF MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Misuzu Hashimoto, Akiyoshi Fukamizu, Tsutomu Nakagawa, Yasuhiko Kizuka
Summary: PRMT1 is crucial for the development of neurons, astrocytes, and oligodendrocytes, requiring further investigation. The relevance of PRMT1 in neurodegenerative diseases will continue to be a hot topic.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Cell Biology
Yi-Fan Huang, Kazuhiro Aoki, Sachiko Akase, Mayumi Ishihara, Yi-Shi Liu, Ganglong Yang, Yasuhiko Kizuka, Shuji Mizumoto, Michael Tiemeyer, Xiao-Dong Gao, Kiyoko F. Aoki-Kinoshita, Morihisa Fujita
Summary: The researchers developed a tool called GlycoMaple to estimate and visualize glycan structures based on gene expression, accelerating glycan analysis and engineering. Through comprehensive glycosylation mapping, gene knockout, and glycomic analysis, the study predicted and compared glycan structures in different cells and tissues.
DEVELOPMENTAL CELL
(2021)
Article
Cell Biology
Rieko Imae, Naoyuki Kuwabara, Hiroshi Manya, Tomohiro Tanaka, Masato Tsuyuguchi, Mamoru Mizuno, Tamao Endo, Ryuichi Kato
Summary: This study elucidates the critical interactions between POMGNT2 and acceptor peptides, revealing the importance of the catalytic and FnIII domains of POMGNT2 for its enzymatic activity.
Article
Biochemistry & Molecular Biology
Tetsuya Hirata, Atsushi Kobayashi, Tamio Furuse, Ikuko Yamada, Masaru Tamura, Hiroyuki Tomita, Yuko Tokoro, Akinori Ninomiya, Yoshitaka Fujihara, Masahito Ikawa, Yusuke Maeda, Yoshiko Murakami, Yasuhiko Kizuka, Taroh Kinoshita
Summary: The GPI-GalNAc side chain is essential for the functions of GPI-APs in mammals, particularly in bone and the brain. Knocking out the initiation enzyme PGAP4 in mice leads to various phenotypes and increased vulnerability to prion diseases, highlighting the protective roles of the GalNAc side chain.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Reina F. Osuka, Tetsuya Hirata, Masamichi Nagae, Miyako Nakano, Hiroyuki Shibata, Ryo Okamoto, Yasuhiko Kizuka
Summary: The N-terminal domain of N-acetylglucosaminyltransferase-V (GnT-V) is crucial for efficient glycosylation and plays a key role in the recognition of glycoprotein substrates. This study revealed that the N domain interacts directly with the substrate polypeptide, providing new insights into the mechanism of substrate-selective biosynthesis of N-glycans.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Rieko Imae, Hiroshi Manya, Tamao Endo
Summary: Both bacteria and mammals contain glycerol phosphate (GroP)-containing glycans, which play crucial roles in bacterial physiology and virulence. The first identification of a GroP-containing glycan in mammals was reported recently, but its biological significance remains largely unknown. Recent progress has been made in elucidating the biosynthetic mechanisms of GroP-containing glycans in mammals and discussing their potential biological role.
Article
Multidisciplinary Sciences
Hideki Tokuoka, Rieko Imae, Hitomi Nakashima, Hiroshi Manya, Chiaki Masuda, Shunsuke Hoshino, Kazuhiro Kobayashi, Dirk J. Lefeber, Riki Matsumoto, Takashi Okada, Tamao Endo, Motoi Kanagawa, Tatsushi Toda
Summary: Ribitol-phosphate modifications are important for the maturation of alpha-dystroglycan, and defects in these modifications can lead to various diseases. This study demonstrates that prodrug treatments, specifically tetraacetylated CDP-ribitol, can ameliorate muscular dystrophy caused by defects in ISPD. These findings provide potential therapeutic options for muscular dystrophy and other glycosylation defects.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Tetsuya Hirata, Misaki Takata, Yuko Tokoro, Miyako Nakano, Yasuhiko Kizuka
Summary: The activity of GnT-V in cells is regulated by changing the maturity of cellular N-glycans. Altering the glycosylation state affects the secretion and protein level of GnT-V, which in turn impacts its promotion of cancer growth and malignancy.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Reina F. Osuka, Masamichi Nagae, Akito Ohuchi, Shiho Ohno, Yoshiki Yamaguchi, Yasuhiko Kizuka
Summary: In this study, it was found through molecular dynamics simulations and biochemical experiments that residues outside the catalytic pocket of GnT-V are likely involved in the recognition of the core part of N-glycan. Additionally, the simulation suggested that UDP binding affects the orientation of the acceptor due to conformational changes. These findings provide new insights into how GnT-V recognizes its glycoprotein substrates.
Article
Biochemistry & Molecular Biology
Rieko Imae, Hiroshi Manya, Hiroki Tsumoto, Yuri Miura, Tamao Endo
Summary: This study revealed the presence of CDP-Gro in mammalian cells and identified ethanolamine-phosphate cytidylyltransferase 2 (PCYT2) as the synthase of CDP-Gro. Knockdown of PCYT2 reduced cellular CDP-Gro levels and increased the expression of functionally glycosylated 1-DG, suggesting an important role for CDP-Gro in regulating 1-DG function in mammals.
JOURNAL OF BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Haruka Kawade, Jyoji Morise, Sushil K. Mishra, Shuta Tsujioka, Shogo Oka, Yasuhiko Kizuka
Summary: This study revealed that the biosynthesis of HNK-1 in the brain and the kidney are differentially regulated by bisecting GlcNAc, with the former being inhibited by the branching sugar. Mechanistically, bisecting GlcNAc suppresses the activity of GlcAT-P but not GlcAT-S, leading to tissue-specific regulation of HNK-1 synthesis.
Article
Biochemistry & Molecular Biology
Masato Kitano, Yasuhiko Kizuka, Tomoaki Sobajima, Miyako Nakano, Kazuki Nakajima, Ryo Misaki, Saki Itoyama, Yoichiro Harada, Akihiro Harada, Eiji Miyoshi, Naoyuki Taniguchi
Summary: Glycosylation is a common posttranslational modification of proteins that is tightly regulated by the subcellular location and transportation of glycosyltransferases. Knockdown of Rab11 results in enhanced sialylation of N-glycans, specifically through the altered localization of the alpha 2,3-sialyltransferase ST3GAL4. This indicates a novel mechanism of glycosyltransferase regulation by Rab11 in post-Golgi compartments.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)