scholarly journals Differential Expression of Multiple Disease-Related Protein Groups Induced by Valproic Acid in Human SH-SY5Y Neuroblastoma Cells

2020 ◽  
Vol 10 (8) ◽  
pp. 545 ◽  
Author(s):  
Tsung-Ming Hu ◽  
Hsiang-Sheng Chung ◽  
Lieh-Yung Ping ◽  
Shih-Hsin Hsu ◽  
Hsin-Yao Tsai ◽  
...  

Valproic acid (VPA) is a multifunctional medication used for the treatment of epilepsy, mania associated with bipolar disorder, and migraine. The pharmacological effects of VPA involve a variety of neurotransmitter and cell signaling systems, but the molecular mechanisms underlying its clinical efficacy is to date largely unknown. In this study, we used the isobaric tags for relative and absolute quantitation shotgun proteomic analysis to screen differentially expressed proteins in VPA-treated SH-SY5Y cells. We identified changes in the expression levels of multiple proteins involved in Alzheimer’s disease, Parkinson’s disease, chromatin remodeling, controlling gene expression via the vitamin D receptor, ribosome biogenesis, ubiquitin-mediated proteolysis, and the mitochondrial oxidative phosphorylation and electron transport chain. Our data indicate that VPA may modulate the differential expression of proteins involved in mitochondrial function and vitamin D receptor-mediated chromatin transcriptional regulation and proteins implicated in the pathogenesis of neurodegenerative diseases.

2018 ◽  
Vol 27 (03) ◽  
pp. 129-134 ◽  
Author(s):  
B. M. Holzapfel ◽  
F. Jakob ◽  
A. A. Kurth ◽  
G. Maier ◽  
K. Horas

SummaryVitamin D deficiency is a global health problem of enormous and increasing dimensions. In the past decades, numerous studies have centered on the role of vitamin D in the pathogenesis and course of many diseases including several types of cancer. Indeed, vitamin D has been widely acknowledged to be involved in the regulation of cell proliferation, differentiation and apoptosis in numerous cancer cells. While the full range of molecular mechanisms involveld in cancer cell growth and progression remains to be elucidated, recent research has deepened our understanding of the processes that may be affected by vitamin D or vitamin D deficiency.In this review, we consider the properties of bone that enable cancer cells to grow and thrive within the skeleton, and the role of vitamin D and the vitamin D receptor in the process of primary and secondary cancer growth in bone.


Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3219 ◽  
Author(s):  
Ahmed El-Sharkawy ◽  
Ahmed Malki

Vitamin D and its active metabolites are important nutrients for human skeletal health. UV irradiation of skin converts 7-dehydrocholesterol into vitamin D3, which metabolized in the liver and kidneys into its active form, 1α,25-dihydroxyvitamin D3. Apart from its classical role in calcium and phosphate regulation, scientists have shown that the vitamin D receptor is expressed in almost all tissues of the body, hence it has numerous biological effects. These includes fetal and adult homeostatic functions in development and differentiation of metabolic, epidermal, endocrine, neurological and immunological systems of the body. Moreover, the expression of vitamin D receptor in the majority of immune cells and the ability of these cells to actively metabolize 25(OH)D3 into its active form 1,25(OH)2D3 reinforces the important role of vitamin D signaling in maintaining a healthy immune system. In addition, several studies have showed that vitamin D has important regulatory roles of mechanisms controlling proliferation, differentiation and growth. The administration of vitamin D analogues or the active metabolite of vitamin D activates apoptotic pathways, has antiproliferative effects and inhibits angiogenesis. This review aims to provide an up-to-date overview on the effects of vitamin D and its receptor (VDR) in regulating inflammation, different cell death modalities and cancer. It also aims to investigate the possible therapeutic benefits of vitamin D and its analogues as anticancer agents.


2018 ◽  
Vol 19 (12) ◽  
pp. 3866 ◽  
Author(s):  
Guo-Qiang Wu ◽  
Jin-Long Wang ◽  
Rui-Jun Feng ◽  
Shan-Jia Li ◽  
Chun-Mei Wang

Salinity is one of the major abiotic stress factors that limit plant growth and crop yield worldwide. To understand the molecular mechanisms and screen the key proteins in response of sugar beet (Beta vulgaris L.) to salt, in the present study, the proteomics of roots and shoots in three-week-old sugar beet plants exposed to 50 mM NaCl for 72 h was investigated by isobaric Tags for Relative and Absolute Quantitation (iTRAQ) technology. The results showed that 105 and 30 differentially expressed proteins (DEPs) were identified in roots and shoots of salt-treated plants compared with untreated plants, respectively. There were 46 proteins up-regulated and 59 proteins down-regulated in roots; and 13 up-regulated proteins and 17 down-regulated proteins found in shoots, respectively. These DEPs were mainly involved in carbohydrate metabolism, energy metabolism, lipid metabolism, biosynthesis of secondary metabolites, transcription, translation, protein folding, sorting, and degradation as well as transport. It is worth emphasizing that some novel salt-responsive proteins were identified, such as PFK5, MDH, KAT2, ACAD10, CYP51, F3H, TAL, SRPR, ZOG, V-H+-ATPase, V-H+-PPase, PIPs, TIPs, and tubulin α-2/β-1 chain. qRT-PCR analysis showed that six of the selected proteins, including BvPIP1-4, BvVP and BvVAP in root and BvTAL, BvURO-D1, and BvZOG in shoot, displayed good correlation between the expression levels of protein and mRNA. These novel proteins provide a good starting point for further research into their functions using genetic or other approaches. These findings should significantly improve the understanding of the molecular mechanisms involved in salt tolerance of sugar beet plants.


2011 ◽  
Vol 200 (3) ◽  
pp. 146-153 ◽  
Author(s):  
Radim Vrzal ◽  
Aneta Doricakova ◽  
Aneta Novotna ◽  
Petr Bachleda ◽  
Michal Bitman ◽  
...  

2021 ◽  
Vol 9 (6) ◽  
pp. 1183
Author(s):  
Nian Wei ◽  
Lirong Song ◽  
Nanqin Gan

Microcystis blooms are the most widely distributed and frequently occurring cyanobacterial blooms in freshwater. Reducing phosphorus is suggested to be effective in mitigating cyanobacterial blooms, while the underlying molecular mechanisms are yet to be elucidated. In the present study, isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics was employed to study the effects of phosphorus depletion on Microcystis aeruginosa FACHB-905. The production of microcystins (MCs), a severe hazard of Microcystis blooms, was also analyzed. In total, 230 proteins were found to be differentially abundant, with 136 downregulated proteins. The results revealed that, upon phosphorus limitation stress, Microcystis aeruginosa FACHB-905 raised the availability of phosphorus primarily by upregulating the expression of orthophosphate transport system proteins, with no alkaline phosphatase producing ability. Phosphorus depletion remarkably inhibited cell growth and the primary metabolic processes of Microcystis, including transcription, translation and photosynthesis, with structures of photosystems remaining intact. Moreover, expression of nitrogen assimilation proteins was downregulated, while proteins involved in carbon catabolism were significantly upregulated, which was considered beneficial for the intracellular balance among carbon, nitrogen and phosphorus. The expression of MC synthetase was not significantly different upon phosphorus depletion, while MC content was significantly suppressed. It is assumed that phosphorus depletion indirectly regulates the production of MC by the inhibition of metabolic processes and energy production. These results contribute to further understanding of the influence mechanisms of phosphorus depletion on both biological processes and MC production in Microcystis cells.


2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Yanqing Wu ◽  
Yuhan Tang ◽  
Yu Jiang ◽  
Daqiu Zhao ◽  
Jiali Shang ◽  
...  

The molecular mechanisms controlling petal shape in a herbaceous peony, Paeonia lactiflora Pall., a popular high-grade cut flower worldwide, remain unclear. Here, we selected inner and outer petals from P. lactiflora ‘ZiFengyu’ with an anemone type as the study object. Using transcriptome sequencing and isobaric tags for relative and absolute quantitation proteome, 979 differentially expressed genes and 266 differentially expressed proteins were detected within the inner and outer petals. Of these, the present study identified a key gene APETALA2 that regulates flower shape development. In addition, we obtained a 1935 bp full-length cDNA sequence of APETALA2 by rapid amplification of cDNA ends amplification. Through further validation using quantitative real-time polymerase chain reaction and Western blot analysis, APETALA2 showed a markedly higher expression in outer than that in inner petals. Therefore, the present study indicates that the increased expression of APETALA2 contributes to the formation of petals in P. lactiflora.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9641-9641
Author(s):  
Analia Rodriguez-Garzotto ◽  
Isabel Ruppen ◽  
M. Pilar Ximenez de Embun ◽  
Lara Iglesias ◽  
Cristina Gravalos ◽  
...  

9641 Background: Hand-foot syndrome (HFS) is a dose-limiting toxicity of capecitabine (CAP), leading to significant morbidity in patients receiving this agent. Interruption or dose reduction of CAP is the only effective strategy. The purpose of our study is to define the pathophysiology and risk factors predictors of CAP-induced HFS. Previously, we had conducted a clinical trial in patients who developed HFS secondary to CAP. Topical heparin was administered in palms and soles of patients four times/day for three weeks (w), evidencing clinical improvement in 99% of patients. Methods: Paired-skin biopsies of palms at baseline and after 3w from 21 patients were obtained. An iTRAQ (isobaric tags for relative and absolute quantitation) proteomics approach was performed to identify molecular pathways associated with HFS reversion. Results: Comparative analysis between baseline and post-treatment skin samples identified 1876 proteins with high confidence (> 99%). The involvement of the identified proteins in biological networks served to characterize molecular pathways associated with HFS reversion. Conclusions: Several proteins identified in this study have a close relationship with keratinocyte terminal differentiation and keratinocyte intercellular strength. Also, we describe differential expression among proteins involved in inflammatory processes, skin immunity and cell death. In summary, our study not only served to uncover molecular mechanisms associated with HFS reversion, but also to reveal the biomarker role of several proteins in this syndrome. [Table: see text]


1996 ◽  
Vol 16 (2) ◽  
pp. 584-592 ◽  
Author(s):  
G A Candeliere ◽  
P W Jurutka ◽  
M R Haussler ◽  
R St-Arnaud

The hormonal form of vitamin D, 1 alpha,25-dihydroxyvitamin D3 [1,25- (OH)2D3], transiently stimulates the transcription of the c-fos proto-oncogene in osteoblastic cells. We have identified and characterized a vitamin D response element (VDRE) in the promoter of c-fos. The 1,25-(OH)2D3-responsive region was delineated between residues -178 and -144 upstream of the c-fos transcription start site. A mutation that inhibited binding to the sequence concomitantly abolished 1,25-(OH)2D3-induced transcriptional responsiveness; similarly, cloning to the site upstream of a heterologous promoter conferred copy-number-dependent vitamin D responsiveness to a reporter gene, demonstrating that we have identified a functional response element. The structure of the c-fos VDRE was found to be unusual. Mutational analysis revealed that the c-fos VDRE does not conform to the direct repeat configuration in which hexameric core-binding sites are spaced by a few nucleotide residues. In contrast, the entire 36-bp sequence was essential for binding. We identified the vitamin D receptor and the retinoid X receptor alpha as components of the complex that bound the c-fos VDRE. However, our results also show that a putative CCAAT-binding transcription factor/nuclear factor 1 (CTF/NF-1) family member bound the response element in conjunction with the nuclear hormone receptors. The expression of this CTF/NF-1 family member appeared restricted to bone cells. These data hint at new molecular mechanisms of action for vitamin D.


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