Analysis of 14-3-3 isoforms expressed in photoreceptors

Inamdar, Shivangi M.; Lankford, Colten K; Laird, Joseph G.; Novbatova, Gulnara; Tatro, Nicole; Whitmore, S. Scott; Scheetz, Todd E.; Baker, Sheila A.

doi:10.1016/j.exer.2018.02.022

Cited by 15 publications

(14 citation statements)

References 55 publications

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“…Specifically, 14-3-3s are small proteins that modulate cell growth and differentiation, regulation of apoptosis and cell cycle. Although the specific role of these proteins in retinal biology is not yet recognized, YWHAQ and YWHAE are the 14-3-3s proteins most highly expressed in the mouse retina and high levels of YWHAE are present in Rod photoreceptors [ 53 ]. Curiously, 14-3-3 proteins were found to interact with PDC, after its light-dependent phosphorylation, indicating that these may participate in facilitating the dark adaptation of the photoreceptor [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

iTRAQ Quantitative Proteomic Analysis of Vitreous from Patients with Retinal Detachment

Santos

Gaspar

Ciordia

et al. 2018

IJMS

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Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition characterized by a physical separation between neurosensory retina and retinal pigment epithelium. Quantitative proteomics can help to understand the changes that occur at the cellular level during RRD, providing additional information about the molecular mechanisms underlying its pathogenesis. In the present study, iTRAQ labeling was combined with two-dimensional LC-ESI-MS/MS to find expression changes in the proteome of vitreous from patients with RRD when compared to control samples. A total of 150 proteins were found differentially expressed in the vitreous of patients with RRD, including 96 overexpressed and 54 underexpressed. Several overexpressed proteins, several such as glycolytic enzymes (fructose-bisphosphate aldolase A, gamma-enolase, and phosphoglycerate kinase 1), glucose transporters (GLUT-1), growth factors (metalloproteinase inhibitor 1), and serine protease inhibitors (plasminogen activator inhibitor 1) are regulated by HIF-1, which suggests that HIF-1 signaling pathway can be triggered in response to RRD. Also, the accumulation of photoreceptor proteins, including phosducin, rhodopsin, and s-arrestin, and vimentin in vitreous may indicate that photoreceptor degeneration occurs in RRD. Also, the accumulation of photoreceptor proteins, including phosducin, rhodopsin, and s-arrestin, and vimentin in vitreous may indicate that photoreceptor degeneration occurs in RRD. Nevertheless, the differentially expressed proteins found in this study suggest that different mechanisms are activated after RRD to promote the survival of retinal cells through complex cellular responses.

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Section: Discussionmentioning

confidence: 99%

iTRAQ Quantitative Proteomic Analysis of Vitreous from Patients with Retinal Detachment

Santos

Gaspar

Ciordia

et al. 2018

IJMS

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“…Similarly, our topological analysis showed that some genes targeted only by HXMMT had many other functions. For example, YWHAB may perform specific functions in rod photoreceptors [ 34 ]. RACK1 may promote the expression of VEGF in endothelial cells and subsequently facilitate angiogenesis [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Approach to Comparatively Predict the Active Ingredients and Molecular Targets of Compound Xueshuantong Capsule and Hexuemingmu Tablet in the Treatment of Proliferative Diabetic Retinopathy

Yao

Xin

Zhan

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Compound Xueshuantong capsule (CXC) and Hexuemingmu tablet (HXMMT) are two important Chinese patent medicines (CPMs) frequently used to treat proliferative diabetic retinopathy (PDR), especially when complicated with vitreous hemorrhage (VH). However, a network pharmacology approach to understand the therapeutic mechanisms of these two CPMs in PDR has not been applied. Objective. To identify differences in the active ingredients between CXC and HXMMT and to comparatively predict and further analyze the molecular targets shared by these CPMs and PDR. Materials and methods. The differentially expressed messenger RNAs (mRNAs) between normal retinal tissues in healthy individuals and active fibrovascular membranes in PDR patients were retrieved from the Gene Expression Omnibus database. The active ingredients of CXC and HXMMT and the targets of these ingredients were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. The intersections of the CPM (CXC and HXMMT) targets and PDR targets were determined. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, and the ingredient-target networks, protein-protein interaction networks, and KEGG-target (KEGG-T) networks were constructed. Results. CXC contains 4 herbs, and HXMMT contains 19. Radix salviae is the only herb common to both. CXC had 34 potential therapeutic targets in PDR, while HXMMT had these 34 and 10 additional targets. Both CPMs shared the following main processes: response to reactive oxygen species and oxidative stress, regulation of blood vessel diameter and size, vasoconstriction, smooth muscle contraction, hemostasis, and blood coagulation. The shared pathways included the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, relaxin signaling pathway, and IL-17 signaling pathway. Conclusions. Both CXC and HXMMT include components effective at treating PDR and affect the following main processes: response to reactive oxygen species and oxidative stress, regulation of blood vessels, and blood coagulation. Radix salviae, the only herb common to both CPMs, contains many useful active ingredients. The PDR-CXC and PDR-HXMMT networks shared 34 common genes (RELA, HSPA8, HSP90AA, HSP90AB1, BRCA, EWSR1, CUL7, HNRNPU, MYC, CTNNB1, MDM2, YWHAZ, CDK2, AR, FN1, HUWE1, TP53, TUBB, EP300, GRB2, VCP, MCM2, EEF1A1, NTRK1, TRAF6, EGFR, PRKDC, SRC, HDAC5, APP, ESR1, AKT1, UBC, and COPS5), and the PDR-HXMMT network has 10 additional genes (RNF2, VNL, RPS27, COPS5, XPO1, PARP1, RACK1, YWHAB, and ITGA4). The top 5 pathways with the highest gene ratio in both networks were the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, relaxin signaling pathway, IL-17 signaling pathway, and focal adhesion. Additional pathways such as neuroactive ligand-receptor interaction, chemokine signaling pathway, and AMPK signaling pathway were enriched with HXMMT targets. Thus, HXMMT has more therapeutic targets shared by different active ingredients and more abundant gene functions than CXC, which may be two major reasons why HXMMT is more strongly recommended than CXC as an auxiliary treatment for new-onset VH secondary to PDR. However, the underlying mechanisms still need to be further explored.

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“…YWHAE protein is widely expressed in eukaryote cells, and has been detected in wheat [19], giant trematodes in goat blood cells [20], liver ukes [21], and mosquitoes [22]. Moreover, in the physiological state of the human body, YWHAE was described as an important element in retinal photoreceptor rod cells [23]. Some researchers have found that YWHAE is also involved in the differentiation of adiposederived mesenchymal stem cells into osteoblasts, enhancing the body's osteogenic ability [24].…”

Section: Discussionmentioning

confidence: 99%

YWHAE Influences the Malignant Behaviour of Ovarian Cancer by Regulating the PI3K/AKT and MAPK Pathways Via HE4

X¹,

Wang²,

Wang³

et al. 2021

Preprint

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Background: Malignant tumours of the female reproductive system threaten the lives and health of women worldwide, with ovarian cancer having the highest mortality rate among all malignant tumours. Based on previous work, this study analysed the expression and role of YWHAE in ovarian epithelial tumours. Methods: The interaction between YWHAE and HE4 was evaluated by immunoprecipitation, western blot analysis, and cellular immunofluorescence. Immunohistochemistry was used to address the relationship between YWHAE expression and clinicopathological parameters and patient prognosis. Changes in cell invasion, epithelial–mesenchymal transition, migration, proliferation, cell cycle, and apoptosis before and after differential expression of YWHAE were also explored in ovarian cancer cell lines and in vivo experiments. Results: YWHAE was found to directly interact with HE4, and its expression was positively correlated with HE4 expression. Moreover, YWHAE higher levels were associated with advanced ovarian cancer cases and with poorer patient outcome. YWHAE was found to enhance the invasion, migration, proliferation, and inhibition of apoptosis of ovarian cancer cells. These biological effects were found to be meditated by the activity of the PI3K/AKT and MAPK signalling pathways.Conclusions: Altogether, this study demonstrates that YWHAE is significantly increased in ovarian cancer tissues, representing a risk factor for the prognosis of ovarian cancer that is positively correlated with HE4 expression. Furthermore, YWHAE and its downstream signals may represent new therapeutic targets to tackle ovarian cancer.

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Analysis of 14-3-3 isoforms expressed in photoreceptors

Cited by 15 publications

References 55 publications

iTRAQ Quantitative Proteomic Analysis of Vitreous from Patients with Retinal Detachment

iTRAQ Quantitative Proteomic Analysis of Vitreous from Patients with Retinal Detachment

Network Pharmacology-Based Approach to Comparatively Predict the Active Ingredients and Molecular Targets of Compound Xueshuantong Capsule and Hexuemingmu Tablet in the Treatment of Proliferative Diabetic Retinopathy

YWHAE Influences the Malignant Behaviour of Ovarian Cancer by Regulating the PI3K/AKT and MAPK Pathways Via HE4

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