scholarly journals Neuroprotective and Mitoprotective Effects of Lemon IntegroPectin on SH-SY5Y Cells

2021 ◽  
Author(s):  
Domenico Nuzzo ◽  
Pasquale Picone ◽  
Costanza Giardina ◽  
Miriana Scordino ◽  
Giuseppa Mudò ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Hydrodynamic Cavitation ◽  
Neuroprotective Activity ◽  
Oxygen Species ◽  
Processing Waste ◽  
Citrus Pectin ◽  
Pectic Substance ◽  
Cellular Processes ◽  
Mitochondrial Regulation

AbstractLemon IntegroPectin obtained via hydrodynamic cavitation of organic lemon processing waste in water shows significant neuroprotective activity in vitro, as first reported in this study investigating the effects of both lemon IntegroPectin and commercial citrus pectin on cell viability, cell morphology, reactive oxygen species (ROS) production and mitochondria perturbation induced by treatment of neuronal SH-SY5Y human cells with H2O2. Mediated by ROS including H2O2 and its derivatives, oxidative stress alters numerous cellular processes, including mitochondrial regulation and cell signaling, propagating cellular injury that leads to incurable neurodegenerative diseases. These results, and the absence of toxicity of this new pectic substance rich in adsorbed flavonoids and terpenes, support further investigations to verify its activity in preventing, retarding, or even curing neurological diseases.

scholarly journals New Neuroprotective Effect of Lemon IntegroPectin on Neuronal Cellular Model

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 669
Author(s):  
Domenico Nuzzo ◽  
Pasquale Picone ◽  
Costanza Giardina ◽  
Miriana Scordino ◽  
Giuseppa Mudò ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Neuroprotective Effect ◽  
Hydrodynamic Cavitation ◽  
Neuroprotective Activity ◽  
Processing Waste ◽  
Citrus Pectin ◽  
Pectic Substance ◽  
Cellular Processes ◽  
Mitochondrial Regulation

Lemon IntegroPectin obtained via hydrodynamic cavitation of organic lemon processing waste in water shows significant neuroprotective activity in vitro, as first reported in this study investigating the effects of both lemon IntegroPectin and commercial citrus pectin on cell viability, cell morphology, reactive oxygen species (ROS) production, and mitochondria perturbation induced by treatment of neuronal SH-SY5Y human cells with H2O2. Mediated by ROS, including H2O2 and its derivatives, oxidative stress alters numerous cellular processes, such as mitochondrial regulation and cell signaling, propagating cellular injury that leads to incurable neurodegenerative diseases. These results, and the absence of toxicity of this new pectic substance rich in adsorbed flavonoids and terpenes, suggest further studies to investigate its activity in preventing, retarding, or even curing neurological diseases.

scholarly journals A gluten-free biscuit fortified with lemon IntegroPectin

2021 ◽  
Author(s):  
Domenico Nuzzo ◽  
Antonino Scurria ◽  
Pasquale Picone ◽  
Alessandro Guiducci ◽  
Mario Pagliaro ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Antioxidant Properties ◽  
Rice Flour ◽  
Hydrodynamic Cavitation ◽  
Neuroprotective Activity ◽  
Gluten Free ◽  
Processing Waste ◽  
Citrus Pectin ◽  
Neuronal Disorders

Abstract We report the first outcomes of producing a gluten-free biscuit by replacing 2.5 wt% of the rice flour used in the preparation of the cookie with lemon IntegroPectin, a new citrus pectin obtained from lemon processing waste via hydrodynamic cavitation showing exceptional antioxidant properties and (in vitro) high neuroprotective activity. The cookie’s friability, palate adhesion, flavor persistency and compactness remain virtually unchanged. Only the sweetness and the smell (flavor) of the functionalized cookie are lower than those of the commercial biscuit. Production of biscuits fortified with this new pectin might result not only in gluten-free and low-calorie cookies but also in a fortified cookie capable to aid in the prevention of chronic disease such as neuronal disorders.

scholarly journals Antioxidant and food additive BHA prevents TNF cytotoxicity by acting as a direct RIPK1 inhibitor

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Tom Delanghe ◽  
Jon Huyghe ◽  
Seungheon Lee ◽  
Dario Priem ◽  
Samya Van Coillie ◽  
...  
Keyword(s):  
Antioxidant Properties ◽  
In Silico Analysis ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Cellular Processes ◽  
Silico Analysis ◽  
Surprising Finding ◽  
Necrosis Factor ◽  
In Cells

AbstractButylate hydroxyanisole (BHA) is a synthetic phenol that is widely utilized as a preservative by the food and cosmetic industries. The antioxidant properties of BHA are also frequently used by scientists to claim the implication of reactive oxygen species (ROS) in various cellular processes, including cell death. We report on the surprising finding that BHA functions as a direct inhibitor of RIPK1, a major signaling hub downstream of several immune receptors. Our in silico analysis predicts binding of 3-BHA, but not 2-BHA, to RIPK1 in an inactive DLG-out/Glu-out conformation, similar to the binding of the type III inhibitor Nec-1s to RIPK1. This predicted superior inhibitory capacity of 3-BHA over 2-BHA was confirmed in cells and using in vitro kinase assays. We demonstrate that the reported protective effect of BHA against tumor necrosis factor (TNF)-induced necroptotic death does not originate from ROS scavenging but instead from direct RIPK1 enzymatic inhibition, a finding that most probably extends to other reported effects of BHA. Accordingly, we show that BHA not only protects cells against RIPK1-mediated necroptosis but also against RIPK1 kinase-dependent apoptosis. We found that BHA treatment completely inhibits basal and induced RIPK1 enzymatic activity in cells, monitored at the level of TNFR1 complex I under apoptotic conditions or in the cytosol under necroptosis. Finally, we show that oral administration of BHA protects mice from RIPK1 kinase-dependent lethality caused by TNF injection, a model of systemic inflammatory response syndrome. In conclusion, our results demonstrate that BHA can no longer be used as a strict antioxidant and that new functions of RIPK1 may emerge from previously reported effects of BHA.

scholarly journals Neuroprotective Effect of 1,4-Naphthoquinones in an In Vitro Model of Paraquat and 6-OHDA-Induced Neurotoxicity

2021 ◽  
Vol 22 (18) ◽  
pp. 9933
Author(s):  
Ekaterina Menchinskaya ◽  
Ekaterina Chingizova ◽  
Evgeny Pislyagin ◽  
Galina Likhatskaya ◽  
Yuri Sabutski ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Radical Scavenging Activity ◽  
Neuronal Cells ◽  
Radical Scavenging ◽  
Reactive Oxygen ◽  
Neuroprotective Activity ◽  
Nonspecific Esterase ◽  
Oxygen Species ◽  
6 Hydroxydopamine

Targeted screening using the MTT cell viability test with a mini-library of natural and synthetic 1,4-naphthoquinones and their derivatives was performed in order to increase the survival of Neuro-2a neuroblastoma cells in in vitro paraquat and 6-hydroxydopamine models of Parkinson’s disease. As a result, 10 compounds were selected that could protect neuronal cells from the cytotoxic effects of both paraquat and 6-hydroxydopamine. The five most active compounds at low concentrations were found to significantly protect the activity of nonspecific esterase from the inhibitory effects of neurotoxins, defend cell biomembranes from lytic destruction in the presence of paraquat and 6-hydroxydopamine, and normalize the cell cycle. The protective effects of these compounds are associated with the suppression of oxidative stress, decreased expression of reactive oxygen species and nitric oxide formation in cells and normalization of mitochondrial function, and restoration of the mitochondrial membrane potential altered by neurotoxins. It was suggested that the neuroprotective activity of the studied 1,4-NQs is attributable to their pronounced antioxidant and free radical scavenging activity and their ability to reduce the amount of reactive oxygen species formed by paraquat and 6-hydroxydopamine action on neuronal cells. The significant correlation between the neuroprotective properties of 1,4-naphthoquinones and Quantitative Structure–Activity Relationship descriptors describing the physicochemical properties of these compounds means that the hydrophobicity, polarity, charge, and shape of the molecules can be of decisive importance in determining the biological activity of studied substances.

Probing the 14-3-3 Isoform-Specificity Profile of Interactions Stabilized by Fusicoccin A

2020 ◽  
Author(s):  
James Frederich ◽  
Ananya Sengupta ◽  
Josue Liriano ◽  
Ewa A. Bienkiewicz ◽  
Brian G. Miller
Keyword(s):  
Protein Interactions ◽  
Neurological Diseases ◽  
Adapter Proteins ◽  
Protein Protein Interactions ◽  
Specific Expression ◽  
Individual Client ◽  
Isoform Specificity ◽  
Fusicoccin A

Fusicoccin A (FC) is a fungal phytotoxin that stabilizes protein–protein interactions (PPIs) between 14-3-3 adapter proteins and their phosphoprotein interaction partners. In recent years, FC has emerged as an important chemical probe of human 14-3-3 PPIs implicated in cancer and neurological diseases. These previous studies have established the structural requirements for FC-induced stabilization of 14-3-3·client phosphoprotein complexes; however, the effect of different 14-3-3 isoforms on FC activity has not been systematically explored. This is a relevant question for the continued development of FC variants because there are seven distinct isoforms of 14-3-3 in humans. Despite their remarkable sequence and structural similarities, a growing body of experimental evidence supports both tissue-specific expression of 14-3-3 isoforms and isoform-specific functions <i>in vivo</i>. Herein, we report the isoform-specificity profile of FC <i>in vitro</i>using recombinant human 14-3-3 isoforms and a focused library of fluorescein-labeled hexaphosphopeptides mimicking the C-terminal 14-3-3 recognition domains of client phosphoproteins targeted by FC in cell culture. Our results reveal modest isoform preferences for individual client phospholigands and demonstrate that FC differentially stabilizes PPIs involving 14-3-3s. Together, these data provide strong motivation for the development of non-natural FC variants with enhanced selectivity for individual 14-3-3 isoforms.

scholarly journals Cockayne syndrome B protein acts as an ATP-dependent processivity factor that helps RNA polymerase II overcome nucleosome barriers

2020 ◽  
Vol 117 (41) ◽  
pp. 25486-25493 ◽  
Author(s):  
Jun Xu ◽  
Wei Wang ◽  
Liang Xu ◽  
Jia-Yu Chen ◽  
Jenny Chong ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Neurological Diseases ◽  
Transcription Elongation ◽  
Cockayne Syndrome ◽  
Stable Complex ◽  
Loss Of Function ◽  
Pol Ii ◽  
Chromatin Remodelers ◽  
Processivity Factor

While loss-of-function mutations in Cockayne syndrome group B protein (CSB) cause neurological diseases, this unique member of the SWI2/SNF2 family of chromatin remodelers has been broadly implicated in transcription elongation and transcription-coupled DNA damage repair, yet its mechanism remains largely elusive. Here, we use a reconstituted in vitro transcription system with purified polymerase II (Pol II) and Rad26, a yeast ortholog of CSB, to study the role of CSB in transcription elongation through nucleosome barriers. We show that CSB forms a stable complex with Pol II and acts as an ATP-dependent processivity factor that helps Pol II across a nucleosome barrier. This noncanonical mechanism is distinct from the canonical modes of chromatin remodelers that directly engage and remodel nucleosomes or transcription elongation factors that facilitate Pol II nucleosome bypass without hydrolyzing ATP. We propose a model where CSB facilitates gene expression by helping Pol II bypass chromatin obstacles while maintaining their structures.

scholarly journals Role of Long Non-Coding RNA Polymorphisms in Cancer Chemotherapeutic Response

2021 ◽  
Vol 11 (6) ◽  
pp. 513
Author(s):  
Zheng Zhang ◽  
Meng Gu ◽  
Zhongze Gu ◽  
Yan-Ru Lou
Keyword(s):  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Cellular Processes ◽  
Dna And Rna ◽  
Chemotherapeutic Response ◽  
Non Coding Rna ◽  
Response To Chemotherapy ◽  
Personalized Oncology ◽  
Long Non Coding Rna

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.

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