scholarly journals Human 2-oxoglutarate-dependent oxygenases: nutrient sensors, stress responders, and disease mediators

2020 ◽  
Vol 48 (5) ◽  
pp. 1843-1858
Author(s):  
Sally C. Fletcher ◽  
Mathew L. Coleman
Keyword(s):  
Dna Damage ◽  
Human Disease ◽  
Cancer Development ◽  
Biological Processes ◽  
Cellular Functions ◽  
Metabolic Intermediates ◽  
Oxidative Reactions ◽  
Biological Substrates ◽  
Cellular Stresses ◽  
Enzyme Class

Fe(II)/2-oxoglutarate (2OG)-dependent oxygenases are a conserved enzyme class that catalyse diverse oxidative reactions across nature. In humans, these enzymes hydroxylate a broad range of biological substrates including DNA, RNA, proteins and some metabolic intermediates. Correspondingly, members of the 2OG-dependent oxygenase superfamily have been linked to fundamental biological processes, and found dysregulated in numerous human diseases. Such findings have stimulated efforts to understand both the biochemical activities and cellular functions of these enzymes, as many have been poorly studied. In this review, we focus on human 2OG-dependent oxygenases catalysing the hydroxylation of protein and polynucleotide substrates. We discuss their modulation by changes in the cellular microenvironment, particularly with respect to oxygen, iron, 2OG and the effects of oncometabolites. We also describe emerging evidence that these enzymes are responsive to cellular stresses including hypoxia and DNA damage. Moreover, we examine how dysregulation of 2OG-dependent oxygenases is associated with human disease, and the apparent paradoxical role for some of these enzymes during cancer development. Finally, we discuss some of the challenges associated with assigning biochemical activities and cellular functions to 2OG-dependent oxygenases.

scholarly journals Recent development of nanoparticles for molecular imaging

2017 ◽  
Vol 375 (2107) ◽  
pp. 20170022 ◽  
Author(s):  
Jonghoon Kim ◽  
Nohyun Lee ◽  
Taeghwan Hyeon
Keyword(s):  
Surface Modification ◽  
Molecular Imaging ◽  
Contrast Agents ◽  
Multimodal Imaging ◽  
High Sensitivity ◽  
Accurate Diagnosis ◽  
Biological Processes ◽  
Future Perspectives ◽  
Cellular Functions ◽  
Diagnosis Of Diseases

Molecular imaging enables us to non-invasively visualize cellular functions and biological processes in living subjects, allowing accurate diagnosis of diseases at early stages. For successful molecular imaging, a suitable contrast agent with high sensitivity is required. To date, various nanoparticles have been developed as contrast agents for medical imaging modalities. In comparison with conventional probes, nanoparticles offer several advantages, including controllable physical properties, facile surface modification and long circulation time. In addition, they can be integrated with various combinations for multimodal imaging and therapy. In this opinion piece, we highlight recent advances and future perspectives of nanomaterials for molecular imaging. This article is part of the themed issue ‘Challenges for chemistry in molecular imaging’.

DNA damage response and repair in pancreatic cancer development and therapy

DNA Repair ◽  
2021 ◽  
pp. 103116
Author(s):  
Parnia Rahnamay Farnood ◽  
Romina Danesh Pazhooh ◽  
Zatollah Asemi ◽  
Bahman Yousefi
Keyword(s):  
Pancreatic Cancer ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Cancer Development ◽  
Damage Response

Defective liver formation and liver cell apoptosis in mice lacking the stress signaling kinase SEK1/MKK4

Development ◽  
1999 ◽  
Vol 126 (3) ◽  
pp. 505-516 ◽  
Author(s):  
H. Nishina ◽  
C. Vaz ◽  
P. Billia ◽  
M. Nghiem ◽  
T. Sasaki ◽  
...  
Keyword(s):  
Dna Damage ◽  
Heat Shock ◽  
Stress Signaling ◽  
Severe Anemia ◽  
Visceral Endoderm ◽  
Survival Signal ◽  
Cellular Stresses ◽  
Massive Apoptosis ◽  
Parenchymal Hepatocytes ◽  
Direct Activator

The stress signaling kinase SEK1/MKK4 is a direct activator of stress-activated protein kinases (SAPKs; also called Jun-N-terminal kinases, JNKs) in response to a variety of cellular stresses, such as changes in osmolarity, metabolic poisons, DNA damage, heat shock or inflammatory cytokines. We have disrupted the sek1 gene in mice using homologous recombination. Sek1(−/−)embryos display severe anemia and die between embryonic day 10.5 (E10.5) and E12.5. Haematopoiesis from yolk sac precursors and vasculogenesis are normal in sek1(−/−)embryos. However, hepatogenesis and liver formation were severely impaired in the mutant embryos and E11.5 and E12.5 sek1(−/−)embryos had greatly reduced numbers of parenchymal hepatocytes. Whereas formation of the primordial liver from the visceral endoderm appeared normal, sek1(−/−) liver cells underwent massive apoptosis. These results provide the first genetic link between stress-responsive kinases and organogenesis in mammals and indicate that SEK1 provides a crucial and specific survival signal for hepatocytes.

scholarly journals Isochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer development

2021 ◽  
Vol 10 (3) ◽  
pp. 1444-1456
Author(s):  
Jinghan Shi ◽  
Fujun Yang ◽  
Nanfeng Zhou ◽  
Yan Jiang ◽  
Yanfeng Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Dna Damage Repair ◽  
Cancer Development ◽  
Damage Repair

scholarly journals Increased Expression of CCN2 in the Red Flashing Light-Induced Myopia in Guinea Pigs

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Hong Wang ◽  
Kang Zhuang ◽  
Lei Gao ◽  
Linna Zhang ◽  
Hongling Yang
Keyword(s):  
Gene Expression ◽  
Animal Model ◽  
Axial Length ◽  
Growth And Development ◽  
Visual Environment ◽  
Biological Processes ◽  
Cellular Functions ◽  
Ocular Growth ◽  
Flashing Light

Visual environment plays an important role in the occurrence of myopia. We previously showed that the different flashing lights could result in distinct effects on the ocular growth and development of myopia. CCN2 has been reported to regulate various cellular functions and biological processes. However, whether CCN2 signaling was involved in the red flashing light-induced myopia still remains unknown. In the present study, we investigated the effects of the red flashing lights exposure on the refraction and axial length of the eyesin vivoand then evaluated their effects on the expression of CCN2 and TGF-βin sclera tissues. Our data showed that the eyes exposed to the red flashing light became more myopic with a significant increase of the axial length and decrease of the refraction. Both CCN2 and TGF-β, as well as p38 MAPK and PI3K, were highly expressed in the sclera tissues exposed to the red flashing light. Both CCN2 and TGF-βwere found to have the same gene expression profilein vivo. In conclusion, our findings found that CCN2 signaling pathway plays an important role in the red flashing light-induced myopiain vivo. Moreover, our study establishes a useful animal model for experimental myopia research.

Cartilage Oligomeric Matrix Protein affects prostate cancer development by altering main cellular functions

Immunobiology ◽  
2016 ◽  
Vol 221 (10) ◽  
pp. 1156
Author(s):  
Konstantinos Papadakos ◽  
Emelie Englund ◽  
Giacomo Canesin ◽  
Emma Persson ◽  
Neelanjan Vishnu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cartilage Oligomeric Matrix Protein ◽  
Matrix Protein ◽  
Cancer Development ◽  
Cellular Functions ◽  
Prostate Cancer Development

Effects of 1800 MHz RF-EMF exposure on DNA damage and cellular functions in primary cultured neurogenic cells

2018 ◽  
Vol 94 (3) ◽  
pp. 295-305 ◽  
Author(s):  
Liling Su ◽  
Aziguli Yimaer ◽  
Zhengping Xu ◽  
Guangdi Chen
Keyword(s):  
Dna Damage ◽  
Cellular Functions

Inflammation and oxidatively induced DNA damage: A synergy leading to cancer development

Cancer ◽  
2021 ◽  
pp. 131-147
Author(s):  
Ioanna Tremi ◽  
Somaira Nowsheen ◽  
Khaled Aziz ◽  
Shankar Siva ◽  
Jessica Ventura ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Development

scholarly journals Epigenetic modifications of histones in cancer

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Zibo Zhao ◽  
Ali Shilatifard
Keyword(s):  
Histone Modifications ◽  
Functional Significance ◽  
Epigenetic Modifications ◽  
Cancer Development ◽  
Clinical Implications ◽  
Biological Processes ◽  
Disease Pathogenesis ◽  
Different Types ◽  
Histone Modifiers ◽  
The Many

AbstractThe epigenetic modifications of histones are versatile marks that are intimately connected to development and disease pathogenesis including human cancers. In this review, we will discuss the many different types of histone modifications and the biological processes with which they are involved. Specifically, we review the enzymatic machineries and modifications that are involved in cancer development and progression, and how to apply currently available small molecule inhibitors for histone modifiers as tool compounds to study the functional significance of histone modifications and their clinical implications.

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