scholarly journals Potential Neuroprotective and Anti-Apoptotic Properties of a Long-Lasting Stable Analog of Ghrelin: an In Vitro Study Using SH-SY5Y Cells

2018 ◽  
pp. 339-346 ◽  
Author(s):  
A. POPELOVÁ ◽  
A. KÁKONOVÁ ◽  
L. HRUBÁ ◽  
J. KUNEŠ ◽  
L. MALETÍNSKÁ ◽  
...  

Neurodegenerative disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), are increasing in prevalence. Currently, there are no effective and specific treatments for these disorders. Recently, positive effects of the orexigenic hormone ghrelin on memory and learning were demonstrated in mouse models of AD and PD. In this study, we tested the potential neuroprotective properties of a stable and long-lasting ghrelin analog, Dpr3ghrelin (Dpr3ghr), in SH-SY5Y neuroblastoma cells stressed with 1.2 mM methylglyoxal (MG), a toxic endogenous by-product of glycolysis, and we examined the impact of Dpr3ghr on apoptosis. Pre-treatment with both 10-5 and 10-7 M Dpr3ghr resulted in increased viability in SH-SY5Y cells (determined by MTT staining), as well as reduced cytotoxicity of MG in these cells (determined by LDH assay). Dpr3ghr increased viability by altering pro-apoptotic and viability markers: Bax was decreased, Bcl-2 was increased, and the Bax/Bcl-2 ratio was attenuated. The ghrelin receptor GHS-R1 and Dpr3ghr-induced activation of PBK/Akt were immuno-detected in SH-SY5Y cells to demonstrate the presence of GHS-R1 and GHS-R1 activation, respectively. We demonstrated that Dpr3ghr protected SH-SY5Y cells against MG-induced neurotoxicity and apoptosis. Our data suggest that stable ghrelin analogs may be candidates for the effective treatment of neurodegenerative disorders.

2007 ◽  
Vol 292 (3) ◽  
pp. E891-E899 ◽  
Author(s):  
Raul M. Luque ◽  
Zhi H. Huang ◽  
Bhumik Shah ◽  
Theodore Mazzone ◽  
Rhonda D. Kineman

Leptin-deficient obese mice ( ob/ob) have decreased circulating growth hormone (GH) and pituitary GH and ghrelin receptor (GHS-R) mRNA levels, whereas hypothalamic GH-releasing hormone (GHRH) and somatostatin (SST) expression do not differ from lean controls. Given the fact that GH is suppressed in diet-induced obesity (a state of hyperleptinemia), it remains to be determined whether the absence of leptin contributes to changes in the GH axis of ob/ob mice. Therefore, to study the impact of leptin replacement on the hypothalamic-pituitary GH axis of ob/ob mice, leptin was infused for 7 days (sc), resulting in circulating leptin levels that were similar to wild-type controls (∼1 ng/ml). Leptin treatment reduced food intake, body weight, and circulating insulin while elevating circulating n-octanoyl ghrelin concentrations. Leptin treatment did not alter hypothalamic GHRH, SST, or GHS-R mRNA levels compared with vehicle-treated controls. However, leptin significantly increased pituitary GH and GHRH-R expression and tended to enhance circulating GH levels, but this latter effect did not reach statistical significance. In vitro, leptin (1 ng/ml, 24 h) did not affect pituitary GH, GHRH-R, or GHS-R mRNA but did enhance GH release. The in vivo effects of leptin on circulating hormone and pituitary mRNA levels were not replicated by pair feeding ob/ob mice to match the food intake of leptin-treated mice. However, leptin did prevent the fall in hypothalamic GHRH mRNA and circulating IGF-I levels observed in pair-fed mice. These results demonstrate that leptin replacement has positive effects on multiple levels of GH axis function in ob/ob mice.


2018 ◽  
Vol 8 (1) ◽  
pp. 20-26
Author(s):  
Asim Rizvi ◽  
Sean T. Fitzgerald ◽  
Kent D. Carlson ◽  
Dan Dragomir Daescu ◽  
Waleed Brinjikji ◽  
...  

Background: “Remote aspiration,” using suction from the proximal internal carotid artery (ICA) to open terminus occlusions, has been reported in small case series. However, it remains unclear whether remote aspiration is feasible for middle cerebral artery occlusions in the setting of potential inflow from communicating arteries. We performed an in vitro study to assess whether suction applied at various locations proximal to an occlusion could successfully aspirate the clot. Methods: A glass model of 4 mm inner diameter (ID) with 1 mm distal narrowing and 2 mm side branch to simulate a communicating artery was constructed. A proximal side branch was placed to simulate inflow from the proximal ICA. The impact of three different-sized catheters (ID 0.088, 0.070, and 0.056 in) on histologically different (red blood cell-cell rich, fibrin-rich, and mixed) clot analogues was tested with the catheter tip placed remotely either distal or proximal to the collateral branch. Aspiration was attempted with (1) open system (flow in both the ICA and the collateral branch, (2) flow arrest with open collateral (no flow in the ICA, but flow in the collateral branch), and (3) closed system (no flow in either the ICA or the collateral branch). The outcome was success or failure of remote aspiration. Results: For the 0.088-in catheter, remote aspiration was successful in all conditions. For the 0.070-in catheter, remote aspiration was unsuccessful without proximal flow arrest, but was successful in all other scenarios. For the 0.056-in catheter, remote aspiration was successful only with complete flow arrest. Conclusions: In a noncollapsible system, remote aspiration can be successfully achieved even in the setting of prominent branch arteries by using relatively large aspiration catheters. Proximal flow arrest may facilitate successful remote aspiration for some catheter sizes.


Author(s):  
Shweta Kishor Sonawane ◽  
Subashchandrabose Chinnathambi

AbstractBackgroundAlzheimer’s disease is a type of dementia denoted by progressive neuronal death due to the accumulation of proteinaceous aggregates of Tau. Post-translational modifications like hyperphosphorylation, truncation, glycation, etc. play a pivotal role in Tau pathogenesis. Glycation of Tau aids in paired helical filament formation and abates its microtubule-binding function. The chemical modulators of Tau PTMs, such as kinase inhibitors and antibody-based therapeutics, have been developed, but natural compounds, as modulators of Tau PTMs are not much explored.MethodsWe applied biophysical and biophysical techniques like fluorescence kinetics, SDS-PAGE, western blot analysis and transmission electron microscopy to investigate the impact of EGCG on Tau glycation in vitro. The effect of glycation on cytoskeleton instability and its EGCG-mediated rescue were studied by immunofluorescence in neuroblastoma cells.ResultsEGCG inhibited methyl glyoxal (MG)-induced Tau glycation in vitro. EGCG potently inhibited MG-induced advanced glycation endproducts formation in neuroblastoma cells as well modulated the localization of AT100 phosphorylated Tau in the cells. In addition to preventing the glycation, EGCG enhanced actin-rich neuritic extensions and rescued actin and tubulin cytoskeleton severely disrupted by MG. EGCG maintained the integrity of the Microtubule Organizing Center (MTOC) stabilized microtubules by Microtubule-associated protein RP/EB family member 1 (EB1).ConclusionsWe report EGCG, a green tea polyphenol, as a modulator of in vitro methylglyoxal-induced Tau glycation and its impact on reducing advanced glycation end products in neuroblastoma cells. We unravel unprecedented function of EGCG in remodeling neuronal cytoskeletal integrity.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Noelle Zurmühl ◽  
Anna Schmitt ◽  
Ulrike Formentini ◽  
Johannes Weiss ◽  
Heike Appel ◽  
...  

Abstract Background Human plasmacytoid dendritic cells (pDC) have a dual role as interferon-producing and antigen-presenting cells. Their relevance for allergic diseases is controversial. and the impact of pDC on allergic immune responses is poorly understood. Methods This in vitro study on human pDC isolated from peripheral blood was designed to compare side by side the uptake of three clinically relevant representative allergens: fluorochrome-labeled house dust mite Der p 1, Bee venom extract from Apis mellifera (Api) and the food allergen OVA analyzed flow cytometry and confocal microscopy. Results We found that the internalization and its regulation by TLR9 ligation was significantly different between allergens in terms of time course and strength of uptake. Api and OVA uptake in pDC of healthy subjects was faster and reached higher levels than Der p 1 uptake. CpG ODN 2006 suppressed OVA uptake and to a lesser extent Der p 1, while Api internalization was not affected. All allergens colocalized with LAMP1 and EEA1, with Api being internalized particularly fast and reaching highest intracellular levels in pDC. Of note, we could not determine any specific differences in antigen uptake in allergic compared with healthy subjects. Conclusions To our knowledge this is the first study that directly compares uptake regulation of clinically relevant inhalative, injective and food allergens in pDC. Our findings may help to explain differences in the onset and severity of allergic reactions as well as in the efficiency of AIT.


2014 ◽  
Vol 56 (8) ◽  
pp. 655-659 ◽  
Author(s):  
Chang-Young Lee ◽  
Seong-Ho Park ◽  
Chang-Hyun Kim ◽  
Goetz Benndorf

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2806 ◽  
Author(s):  
Evdokia K. Mitsou ◽  
Georgia Saxami ◽  
Emmanuela Stamoulou ◽  
Evangelia Kerezoudi ◽  
Eirini Terzi ◽  
...  

Alterations of gut microbiota are evident during the aging process. Prebiotics may restore the gut microbial balance, with β-glucans emerging as prebiotic candidates. This study aimed to investigate the impact of edible mushrooms rich in β-glucans on the gut microbiota composition and metabolites by using in vitro static batch culture fermentations and fecal inocula from elderly donors (n = 8). Pleurotus ostreatus, P. eryngii, Hericium erinaceus and Cyclocybe cylindracea mushrooms derived from various substrates were examined. Gut microbiota composition (quantitative PCR (qPCR)) and short-chain fatty acids (SCFAs; gas chromatography (GC)) were determined during the 24-h fermentation. P. eryngii induced a strong lactogenic effect, while P. ostreatus and C. cylindracea induced a significant bifidogenic effect (p for all <0.05). Furthermore, P. eryngii produced on wheat straw and the prebiotic inulin had comparable Prebiotic Indexes, while P. eryngii produced on wheat straw/grape marc significantly increased the levels of tested butyrate producers. P. ostreatus, P. eryngii and C. cylindracea had similar trends in SCFA profile; H. erinaceus mushrooms were more diverse, especially in the production of propionate, butyrate and branched SCFAs. In conclusion, mushrooms rich in β-glucans may exert beneficial in vitro effects in gut microbiota and/or SCFAs production in elderly subjects.


2020 ◽  
Vol 47 (8) ◽  
pp. 3691-3702 ◽  
Author(s):  
Elisabeth Mara ◽  
Monika Clausen ◽  
Suphalak Khachonkham ◽  
Simon Deycmar ◽  
Clara Pessy ◽  
...  

2013 ◽  
Vol 37 (4) ◽  
pp. 403-406 ◽  
Author(s):  
S Tamilselvam ◽  
MJ Divyanand ◽  
P Neelakantan

Objective: This aim of this study was at compare the fibroblast cytotoxicicty of four restorative materials - a conventional glass ionomer cement (GC Fuji Type II GIC), a ceramic reinforced glass ionomer cement (Amalgomer), a giomer (Beautifil II) and a resin composite (Filtek Z350) at three different time periods (24, 48 and 72 hours). Method: The succinyl dehydrogenase (MTT) assay was employed. Cylindrical specimens of each material (n=15) were prepared and stored in Dulbecco's modified Eagle medium, following which L929 fibroblasts were cultured in 96 well plates. After 24 hours of incubation, the MTT assay was performed to detect the cell viability. The method was repeated after 48 and 72 hours. The impact of materials and exposure times on cytotoxicity of fibroblasts was statistically analyzed using two way ANOVA (P=0.05). Results: Both time and material had an impact on cell viability, with giomer demonstrating the maximum cell viability at all time periods. The cell viability in the giomer group was significantly different from all other materials at 24 and 72 hours (P&lt;0.05), while at 48 hours giomer was significantly different only with resin composite (P&lt;0.05). Conclusions: Giomers showed better biocompatibility than conventional and ceramic reinforced glass ionomer cements and, resin composite. Ceramic reinforced glass ionomer demonstrated superior biocompatibility compared to conventional glass ionomer.


Sign in / Sign up

Export Citation Format

Share Document