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Sailendra Singh, Pallavi Pandey, Sumit Ghosh, Suchitra Banerjee
Andrographolide (AD) is the time-honoured pharmacologically active constituent of the traditionally renowned medicinal plant-Andrographis paniculata. Advancements in the target-oriented drug discovery process have further unravelled the immense therapeutic credibility of another unique molecule-neoandrographolide (NAD). The escalated market demand of these anti-cancer diterpenes is increasingly facing unrelenting hurdles of demand and supply disparity, attributable to their limited yield. Callus and adventitious root cultures were generated to explore their biosynthetic potentials which first time revealed NAD production along with AD...
March 20, 2018: Protoplasma
Bingyang Dai, Qiangqiang Li, Xiaoxiao Song, Yuxiang Ge, Jing Wu, Kaijia Zhang, Chao Wang, Yifeng Zhang, Huajian Teng, Chaojun Li, Qing Jiang
Bone fracture healing is achieved through the proliferation and differentiation of stem cells, while bone marrow stem cells (BMSCs) contribute to endochondral ossification. During fracture healing, mesenchymal progenitor cells first form a cartilaginous blastema that becomes vascularized to recruit precursor cells of osteoblasts through the bone morphogenetic protein 2 (Bmp2)/Smad-dependent Runx2 pathway. Statins deplete geranylgeranyl diphosphate (GGPP), which participates in the regulation of BMSCs differentiation, through the inhibition of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, leading to impaired protein geranylgeranylation, which strongly impacts the bone synthesis induced by Bmp2...
March 2018: Journal of Bone and Mineral Metabolism
Wen-Jun Jia, Shan Jiang, Qiao-Li Tang, Di Shen, Bin Xue, Wen Ning, Chao-Jun Li
G proteins play essential roles in regulating fetal lung development, and any defects in their expression or function (eg, activation or posttranslational modification) can lead to lung developmental malformation. Geranylgeranyl diphosphate synthase (GGPPS) can modulate protein prenylation that is required for protein membrane-anchoring and activation. Here, we report that GGPPS regulates fetal lung branching morphogenesis possibly through controlling K-Ras prenylation during fetal lung development. GGPPS was continuously expressed in lung epithelium throughout whole fetal lung development...
June 2016: American Journal of Pathology
Jun Li, Lintao Bi, Zhangzhen Shi, Yanxia Sun, Yumei Lin, Hui Shao, Zhenxing Zhu
We aimed to elucidate the potential mechanisms of long non-coding RNAs (lncRNAs) in the progression of non-small cell lung cancer (NSCLC). The microarray datasets of GSE37764, including 3 primary NSCLC tumors and 3 matched normal tissues isolated from 6 Korean female never-smokers, were downloaded from Gene Expression Omnibus database. The differentially expressed lncRNAs and mRNA in NSCLC samples were identified using NOISeq package. Co-expression network of differentially expressed lncRNAs and mRNA was established...
June 2016: Pathology, Research and Practice
Nhu-Thuy Trinh, Toshiharu Yamashita, Kinuko Ohneda, Kenichi Kimura, Georgina To'a Salazar, Fujio Sato, Osamu Ohneda
The prevalence of type 2 diabetes mellitus (T2DM), which leads to diabetic complications, has been increasing worldwide. The possible applications of T2DM-derived stem cells in cell therapy are limited because their characteristics are still not fully understood. In this study, we characterized adipose tissue-derived mesenchymal stem cells (AT-MSCs) from diabetic patients (dAT-MSCs) and found that insulin receptor substrate-1 (IRS-1) was highly phosphorylated at serine 636/639 in dAT-MSCs. Moreover, we found that early growth response factor-1 (EGR-1) and its target genes of PTEN and GGPS1 were highly expressed in dAT-MSCs in comparison to healthy donor-derived AT-MSCs (nAT-MSCs)...
May 15, 2016: Stem Cells and Development
Aleksandra A Pandyra, Peter J Mullen, Carolyn A Goard, Elke Ericson, Piyush Sharma, Manpreet Kalkat, Rosemary Yu, Janice T Pong, Kevin R Brown, Traver Hart, Marinella Gebbia, Karl S Lang, Guri Giaever, Corey Nislow, Jason Moffat, Linda Z Penn
The mevalonate (MVA) pathway is often dysregulated or overexpressed in many cancers suggesting tumor dependency on this classic metabolic pathway. Statins, which target the rate-limiting enzyme of this pathway, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), are promising agents currently being evaluated in clinical trials for anti-cancer efficacy. To uncover novel targets that potentiate statin-induced apoptosis when knocked down, we carried out a pooled genome-wide short hairpin RNA (shRNA) screen. Genes of the MVA pathway were amongst the top-scoring targets, including sterol regulatory element binding transcription factor 2 (SREBP2), 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (HMGCS1) and geranylgeranyl diphosphate synthase 1 (GGPS1)...
September 29, 2015: Oncotarget
Willy B Suwarno, Kevin V Pixley, Natalia Palacios-Rojas, Shawn M Kaeppler, Raman Babu
Genome-wide association analysis in CIMMYT's association panel revealed new favorable native genomic variations in/nearby important genes such as hydroxylases and CCD1 that have potential for carotenoid biofortification in maize. Genome-wide association studies (GWAS) have been used extensively to identify allelic variation for genes controlling important agronomic and nutritional traits in plants. Provitamin A (proVA) enhancing alleles of lycopene epsilon cyclase (LCYE) and β-carotene hydroxylase 1 (CRTRB1), previously identified through candidate-gene based GWAS, are currently used in CIMMYT's maize breeding program...
May 2015: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
G C M Moreira, T F Godoy, C Boschiero, A Gheyas, G Gasparin, S C S Andrade, M Paduan, H Montenegro, D W Burt, M C Ledur, L L Coutinho
Abdominal fat content is an economically important trait in commercially bred chickens. Although many quantitative trait loci (QTL) related to fat deposition have been detected, the resolution for these regions is low and functional variants are still unknown. The current study was conducted aiming at increasing resolution for a region previously shown to have a QTL associated with fat deposition, to detect novel variants from this region and to annotate those variants to delineate potentially functional ones as candidates for future studies...
April 2015: Animal Genetics
Nicholas J Ruppel, Kelsey N Kropp, Phillip A Davis, Arielle E Martin, Darron R Luesse, Roger P Hangarter
UNLABELLED:PREMISE OF THE STUDY: Within plastids, geranylgeranyl diphosphate synthase is a key enzyme in the isoprenoid biosynthetic pathway that catalyzes the formation of geranylgeranyl diphosphate, a precursor molecule to several biochemical pathways including those that lead into the biosynthesis of carotenoids and abscisic acid, prenyllipids such as the chlorophylls, and diterpenes such as gibberellic acid. • METHODS: We have identified mutants in the GERANYLGERANYL DIPHOSPHATE SYNTHASE 1 (GGPS1) gene, which encodes the major plastid-localized enzyme geranylgeranyl diphosphate synthase in Arabidopsis thaliana...
October 2013: American Journal of Botany
Hyung Jin Choi, Ji Yeob Choi, Sun Wook Cho, Daehee Kang, Ki Ok Han, Sang Wan Kim, Seong Yeon Kim, Yoon-Sok Chung, Chan Soo Shin
PURPOSE: Genetic factor is an important predisposing element influencing the susceptibility to osteoporosis and related complications. The purpose of the present study is to investigate whether genetic polymorphisms of farnesyl diphosphate synthase (FDPS) or geranylgeranyl diphosphate synthase (GGPS) genes were associated with the response to bisphosphonate therapy. MATERIALS AND METHODS: In the present study, 144 Korean women with osteoporosis were included. Among 13 genetic polymorphisms found within the FDPS and GGPS1 gene, 4 genetic polymorphisms with frequencies > 5% were selected for further study...
March 2010: Yonsei Medical Journal
K Okada, T Saito, T Nakagawa, M Kawamukai, Y Kamiya
Geranylgeranyl diphosphate (GGPP) is the precursor for the biosynthesis of gibberellins, carotenoids, chlorophylls, isoprenoid quinones, and geranylgeranylated proteins in plants. There is a small gene family for GGPP synthases encoding five isozymes and one related protein in Arabidopsis, and all homologs have a putative localization signal to translocate into specific subcellular compartments. Using a synthetic green fluorescent protein (sGFP), we studied the subcellular localization of these GGPP synthases...
April 2000: Plant Physiology
T Kainou, K Kawamura, K Tanaka, H Matsuda, M Kawamukai
E,E,E-Geranylgeranyl diphosphate (GGPP) is an important precursor of carotenoids and geranylgeranylated proteins such as small G proteins. In this study, we have identified mouse and human GGPP synthase genes. Sequence analysis showed that mouse and human GGPP synthases share a high level of amino acid identity (94%) with each other, and share a high level of similarity (45-50%) with GGPP synthases of lower eukaryotes, but only weak similarity (22-31%) to plant and prokaryotic GGPP synthases. Both of the newly identified GGPP synthase genes from mouse and human were expressed in Escherichia coli, and their gene products displayed GGPP synthase activity when isopentenyl diphosphate and farnesyl diphosphate were used as substrates...
March 25, 1999: Biochimica et Biophysica Acta
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