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Yan Huang, Zhiping Hu
Cerebral ischemia/reperfusion-induced injury plays a significant role in the development of multi-subcellular organelles injury after ischemic stroke. UBIAD1 was discovered originally as a potential tumor suppressor protein. Recently, analysis of UBIAD1 has indicated it is a prenyltransferase enzyme for both non-mitochondrial CoQ10 and vitamin K2 production. Further, UBIAD1 has been localized to multiple subcellular organelles. Particularly, UBIAD1 plays an important role in the regulation of oxidative stress, apoptosis and cell proliferation, cholesterol and lipid metabolism, which was closely associated with the cerebral ischemic/reperfusion mechanism...
April 16, 2018: Journal of Cellular Physiology
Koji Kitazawa, Koichi Wakimasu, Kanae Kayukawa, Manabu Sugimoto, Junko Nakai, Jayne S Weiss, Morio Ueno, Chie Sotozono, Shigeru Kinoshita
PURPOSE: To investigate the long-term surgical outcome after penetrating keratoplasty in 5 patients from 1 pedigree with Schnyder corneal dystrophy (SCD), resulting from the same UbiA prenyltransferase domain containing 1 (UBIAD1) mutation. METHODS: This retrospective study involved 6 eyes of 5 patients who underwent penetrating keratoplasty for treatment of SCD. Postoperative surgical outcome measures included the analysis of best-corrected visual acuity (BCVA), corneal endothelial cell density, and the rates of corneal graft rejection and disease recurrence...
May 2018: Cornea
Maytham A Dragh, Zhiliang Xu, Zainab S Al-Allak, Ling Hong
Previous studies have established the anticancer effect of vitamin K2 (VK2). However, its effect on lymphoma induced by UBIAD1/heix mutation in Drosophila remains unknown. Therefore, we aimed to develop an in vivo model of lymphoma for the precise characterization of lymphoma phenotypes. We also aimed to improve the understanding of the mechanisms that underlie the preventative effects of VK2 on lymphoma. Our results demonstrated that VK2 prevents lymphoma by acting as an electron carrier and by correcting the function and structure of mitochondria by inhibiting mitochondrial reactive oxygen species production mtROS...
December 6, 2017: Scientific Reports
Marc M Schumacher, Dong-Jae Jun, Brittany M Johnson, Russell A DeBose-Boyd
UBIAD1 (UbiA prenyltransferase domain-containing protein-1) utilizes geranylgeranyl pyrophosphate (GGpp) to synthesize vitamin K2 We previously reported that sterols stimulate binding of UBIAD1 to endoplasmic reticulum (ER)-localized 3-hydroxy-3-methylglutaryl (HMG) CoA reductase. UBIAD1 binding inhibits sterol-accelerated, ER-associated degradation (ERAD) of reductase, one of several mechanisms for feedback control of this rate-limiting enzyme in the branched pathway that produces cholesterol and nonsterol isoprenoids such as GGpp...
January 5, 2018: Journal of Biological Chemistry
Brittany M Johnson, Russell A DeBose-Boyd
Accelerated ubiquitination and subsequent endoplasmic reticulum (ER)-associated degradation (ERAD) constitute one of several mechanisms for feedback control of HMG CoA reductase, the rate-limiting enzyme in synthesis of cholesterol and nonsterol isoprenoids. This ERAD is initiated by the accumulation of certain sterols in ER membranes, which trigger binding of reductase to ER membrane proteins called Insigs. Insig-associated ubiquitin ligases facilitate ubiquitination of reductase, marking the enzyme for extraction across the ER membrane through a reaction that is augmented by nonsterol isoprenoids...
November 7, 2017: Seminars in Cell & Developmental Biology
Bingju Yan, Yingxian Sun, Jun Wang
UbiA prenyltransferase domain containing 1 (UBIAD1) is closely associated with cardiovascular diseases. However, at the cellular level, little is known about how UBIAD1 is expressed and functions in cardiomyocyte hypertrophy. The aim of the present study was to investigate the expression and role of UBIAD1 in angiotensin II (Ang II)‑induced hypertrophy in AC16 cardiomyoblast cells. The loss‑of‑function approach was used to knock down UBIAD1 in vehicle‑ and Ang II‑stimulated AC16 cells. The levels of atrial natriuretic factor (ANF) and caspase-3 were measured and compared between vehicle‑ and Ang II‑treated AC16 cells pretreated with control siRNA or siRNA against UBIAD1...
November 2017: Molecular Medicine Reports
Kristin M McCabe, Sarah L Booth, Xueyan Fu, Emilie Ward, Michael A Adams, Rachel M Holden
BACKGROUND: Patients with chronic kidney disease (CKD) have very high levels of uncarboxylated, inactive, extra-hepatic vitamin K-dependent proteins measured in circulation, putting them at risk for complications of vitamin K deficiency. The major form of vitamin K found in the liver is phylloquinone (K1). Menaquinone-4 (MK-4) is the form of vitamin K that is preferentially found in extra-hepatic tissues. METHODS: In the present study, we assessed tissue concentrations of K1 and MK-4 and the expression of vitamin K-related genes in a rat model of adenine-induced CKD...
2017: American Journal of Nephrology
Toshio Okano
Vitamin K is a cofactor for γ-glutamyl carboxylase, which catalyzes the posttranslational conversion of specific glutamyl residues to γ-carboxyglutamyl residues in a variety of vitamin K-dependent proteins (VKDPs) involved in blood coagulation, bone and cartilage metabolism, signal transduction, and cell proliferation. Despite the great advances in the genetic, structural, and functional studies of VKDPs as well as the enzymes identified as part of the vitamin K cycle which enable it to be repeatedly recycled within the cells, little is known of the identity and roles of key regulators of vitamin K metabolism in mammals and humans...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Benjamin R Lin, Ricardo F Frausto, Rosalind C Vo, Stephan Y Chiu, Judy L Chen, Anthony J Aldave
Purpose. To report the identification of the first de novo UBIAD1 missense mutation in an individual with Schnyder corneal dystrophy (SCD). Methods. A slit lamp examination was performed on a 47-year-old woman without a family history of corneal disorders. The proband's parents, two sisters, and son were also examined and genomic DNA from all six individuals was collected. The exons and exon-intron boundaries of UBIAD1 were screened using Sanger sequencing. Identified mutations were screened for in 200 control chromosomes...
2016: Journal of Ophthalmology
Marc M Schumacher, Dong-Jae Jun, Youngah Jo, Joachim Seemann, Russell A DeBose-Boyd
UbiA prenyltransferase domain-containing protein-1 (UBIAD1) utilizes geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K2 subtype menaquinone-4. Previously, we found that sterols trigger binding of UBIAD1 to endoplasmic reticulum (ER)-localized HMG-CoA reductase, the rate-limiting enzyme in synthesis of cholesterol and nonsterol isoprenoids, including GGpp. This binding inhibits sterol-accelerated degradation of reductase, which contributes to feedback regulation of the enzyme. The addition to cells of geranylgeraniol (GGOH), which can become converted to GGpp, triggers release of UBIAD1 from reductase, allowing for its maximal degradation and permitting ER-to-Golgi transport of UBIAD1...
July 2016: Journal of Lipid Research
Sha Liu, Wang Guo, Xue Han, Wendi Dai, Zongli Diao, Wenhu Liu
Vascular calcification is an important risk factor associated with mortality among patients with chronic kidney disease. Intracellular cholesterol metabolism is involved in the process of vascular cell calcification. In this study, we investigated the role of UbiA prenyltransferase domain containing 1 (UBIAD1) in intracellular cholesterol metabolism and vascular cell calcification, and identified its subcellular location. Primary human umbilical vein smooth muscle cells (HUVSMCs) were incubated with either growth medium (1...
2016: PloS One
Xiaolei Xie, Xian Man, Zuobin Zhu, Dejian Yuan, Shi Huang
OBJECTIVE: The aim of this study was to investigate the shared molecular pathways of obesity and cancer by exploring the role of RIZ1 in obesity and the phospatidylinositol 3-kinase (PI3K)/V-Akt murine thymoma viral oncogene homolog (PKB) (AKT)/mechanistic target of rapamycin (mTOR) pathway. METHODS: Male wild type (WT) and Riz1(-/-) mice (KO) were fed a standard diet (STD) or a high-fat (HF) diet for up to 8 months. These mice were studied for phenotypic and molecular changes...
February 2016: Obesity
Andrew Woolston, Nardnisa Sintupisut, Tzu-Pin Lu, Liang-Chuan Lai, Mong-Hsun Tsai, Eric Y Chuang, Chen-Hsiang Yeang
Lung adenocarcinoma possesses distinct patterns of EGFR/KRAS mutations between East Asian and Western, male and female patients. However, beyond the well-known EGFR/KRAS distinction, gender and ethnic specific molecular aberrations and their effects on prognosis remain largely unexplored. Association modules capture the dependency of an effector molecular aberration and target gene expressions. We established association modules from the copy number variation (CNV), DNA methylation and mRNA expression data of a Taiwanese female cohort...
August 14, 2015: Oncotarget
Yoshihisa Hirota, Kimie Nakagawa, Natsumi Sawada, Naoko Okuda, Yoshitomo Suhara, Yuri Uchino, Takashi Kimoto, Nobuaki Funahashi, Maya Kamao, Naoko Tsugawa, Toshio Okano
UbiA prenyltransferase domain-containing protein 1 (UBIAD1) plays a significant role in vitamin K2 (MK-4) synthesis. We investigated the enzymological properties of UBIAD1 using microsomal fractions from Sf9 cells expressing UBIAD1 by analysing MK-4 biosynthetic activity. With regard to UBIAD1 enzyme reaction conditions, highest MK-4 synthetic activity was demonstrated under basic conditions at a pH between 8.5 and 9.0, with a DTT ≥0.1 mM. In addition, we found that geranyl pyrophosphate and farnesyl pyrophosphate were also recognized as a side-chain source and served as a substrate for prenylation...
2015: PloS One
Nobuaki Funahashi, Yoshihisa Hirota, Kimie Nakagawa, Natumi Sawada, Masato Watanabe, Yoshitomo Suhara, Toshio Okano
Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K1) and a series of bacterial menaquionones (MK-n; vitamin K2). Menadione (vitamin K3) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line...
May 1, 2015: Biochemical and Biophysical Research Communications
Marc M Schumacher, Rania Elsabrouty, Joachim Seemann, Youngah Jo, Russell A DeBose-Boyd
Schnyder corneal dystrophy (SCD) is an autosomal dominant disorder in humans characterized by abnormal accumulation of cholesterol in the cornea. SCD-associated mutations have been identified in the gene encoding UBIAD1, a prenyltransferase that synthesizes vitamin K2. Here, we show that sterols stimulate binding of UBIAD1 to the cholesterol biosynthetic enzyme HMG CoA reductase, which is subject to sterol-accelerated, endoplasmic reticulum (ER)-associated degradation augmented by the nonsterol isoprenoid geranylgeraniol through an unknown mechanism...
March 5, 2015: ELife
Yan Xia, Samira Zohra Midoun, Zhiliang Xu, Ling Hong
The Drosophila heixuedian (heix) is the ortholog of human UBIAD1 gene (a.k.a TERE1). The protein product of UBIAD1/heix has multiple enzymatic activities, including the vitamin K2 and the non-mitochondrial CoQ10 biosynthesis. However, the expression pattern of UBIAD1/Heix during metazoan development has not been systematically studied. In this paper, we found that loss of function of heix resulted in pathological changes of larval hematopoietic system, including lymph gland hypertrophy, hemocyte overproliferation and aberrant differentiation, and melanin mass formation...
February 15, 2015: Developmental Biology
Kimie Nakagawa, Natsumi Sawada, Yoshihisa Hirota, Yuri Uchino, Yoshitomo Suhara, Tomoka Hasegawa, Norio Amizuka, Tadashi Okamoto, Naoko Tsugawa, Maya Kamao, Nobuaki Funahashi, Toshio Okano
UbiA prenyltransferase domain containing 1 (UBIAD1) is a novel vitamin K2 biosynthetic enzyme screened and identified from the human genome database. UBIAD1 has recently been shown to catalyse the biosynthesis of Coenzyme Q10 (CoQ10) in zebrafish and human cells. To investigate the function of UBIAD1 in vivo, we attempted to generate mice lacking Ubiad1, a homolog of human UBIAD1, by gene targeting. Ubiad1-deficient (Ubiad1(-/-)) mouse embryos failed to survive beyond embryonic day 7.5, exhibiting small-sized body and gastrulation arrest...
2014: PloS One
Hua Huang, Elena J Levin, Shian Liu, Yonghong Bai, Steve W Lockless, Ming Zhou
Membrane-embedded prenyltransferases from the UbiA family catalyze the Mg2+-dependent transfer of a hydrophobic polyprenyl chain onto a variety of acceptor molecules and are involved in the synthesis of molecules that mediate electron transport, including Vitamin K and Coenzyme Q. In humans, missense mutations to the protein UbiA prenyltransferase domain-containing 1 (UBIAD1) are responsible for Schnyder crystalline corneal dystrophy, which is a genetic disease that causes blindness. Mechanistic understanding of this family of enzymes has been hampered by a lack of three-dimensional structures...
July 2014: PLoS Biology
Anna K Nowinska, Edward Wylegala, Sławomir Teper, Anita Lyssek-Boron, Pasquale Aragona, Anna M Roszkowska, Antonio Micali, Antonina Pisani, Domenico Puzzolo
PURPOSE: The aim of this study was to analyze the corneal morphology features and define mutations in the UbiA prenyltransferase domain-containing 1 (UBIAD1) gene in patients with Schnyder corneal dystrophy from a Polish population. METHODS: Five affected and 15 unaffected members originating from 3 families with Schnyder corneal dystrophy were included in the study. Phenotype analysis consisted of visual acuity, slit-lamp biomicroscopy with photography, time domain optical coherence tomography, spectral domain optical coherence tomography, and confocal microscopy...
May 2014: Cornea
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