scholarly journals Amyloid-Beta Induces Different Expression Pattern of Tissue Transglutaminase and Its Isoforms on Olfactory Ensheathing Cells: Modulatory Effect of Indicaxanthin

2021 ◽  
Vol 22 (7) ◽  
pp. 3388
Author(s):  
Agata Campisi ◽  
Giuseppina Raciti ◽  
Giovanni Sposito ◽  
Rosaria Grasso ◽  
Maria A. Chiacchio ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Expression Pattern ◽  
Amyloid Beta ◽  
Tissue Transglutaminase ◽  
Olfactory Ensheathing Cells ◽  
Apoptotic Pathway ◽  
Expression Levels ◽  
Pathway Activation ◽  
Ensheathing Cells ◽  
Pre Treatment

Herein, we assessed the effect of full native peptide of amyloid-beta (Aβ) (1-42) and its fragments (25-35 and 35-25) on tissue transglutaminase (TG2) and its isoforms (TG2-Long and TG2-Short) expression levels on olfactory ensheathing cells (OECs). Vimentin and glial fibrillary acid protein (GFAP) were also studied. The effect of the pre-treatment with indicaxanthin from Opuntia ficus-indica fruit on TG2 expression levels and its isoforms, cell viability, total reactive oxygen species (ROS), superoxide anion (O2−), and apoptotic pathway activation was assessed. The levels of Nestin and cyclin D1 were also evaluated. Our findings highlight that OECs exposure to Aβ(1-42) and its fragments induced an increase in TG2 expression levels and a different expression pattern of its isoforms. Indicaxanthin pre-treatment reduced TG2 overexpression, modulating the expression of TG2 isoforms. It reduced total ROS and O2− production, GFAP and Vimentin levels, inhibiting apoptotic pathway activation. It also induced an increase in the Nestin and cyclin D1 expression levels. Our data demonstrated that indicaxanthin pre-treatment stimulated OECs self-renewal through the reparative activity played by TG2. They also suggest that Aβ might modify TG2 conformation in OECs and that indicaxanthin pre-treatment might modulate TG2 conformation, stimulating neural regeneration in Alzheimer’s disease.

scholarly journals Amyloid Beta Exposure on Olfactory Ensheathing Cells Induces Different Expression Pattern of Tissue Transglutaminase and Its Isoforms: Modulatory Effect of Indicaxanthin

2021 ◽  
Author(s):  
Agatina Campisi ◽  
Giuseppina Raciti ◽  
Giovanni Sposito ◽  
Rosaria Grasso ◽  
Maria Assunta Chiacchio ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Amyloid Beta ◽  
Tissue Transglutaminase ◽  
Olfactory Ensheathing Cells ◽  
Cyclin D ◽  
Apoptotic Pathway ◽  
Expression Levels ◽  
Pathway Activation ◽  
Ensheathing Cells ◽  
Pre Treatment

Abstract Background Alzhèimer Disease (AD) is characterized by intracellular and extracellular protein aggregates in the brain, including amyloid-beta (Aβ). Aβ is a substrate for tissue transglutaminase (TG2), an ubiquitarian calcium-dependent protein that induces Aβ oligomerization and aggregation. We assessed the effect of full native peptide of Aβ(1–42), the fragments (25–35 and 35–25) on TG2 expression levels and its isoforms (Long and Short) on Olfactory Ensheathing Cells (OECs). The levels of cytoskeletal proteins, Vimentin and Glial Fibrillary Acid Protein (GFAP), were also studied. The effect of the pre-treatment with Indicaxanthin on cell viability, total Reactive Oxygen Species (ROS), superoxide anion (O2−) and apoptotic pathway activation was assessed. Since Nestin is co-expressed in pluripotent stem cells with cyclin D1, their levels were evaluated. Methods Mouse primary OECs were exposed to 10 µM Aβ(1–42) or Aβ(25–35) or Aβ(35–25) for 24 h both in the absence and in the presence of Indicaxanthin. TG2 and its isoforms were evaluated through Confocal Laser Scanning Microscopy and Western Blot analysis. Data were statistically analysed using one-way analysis of variance followed by post hoc Holm–Sidak. Results Our findings highlight that OEC exposure to Aβ(1–42) and its fragments induced an increase of TG2 levels and the different expression pattern of its isoforms. Indicaxanthin pre-treatment reduced TG2 over-expression differently modulating its isoforms, following Aβ exposure of the cells. It was also able to prevent total ROS and O2−production, to reduce GFAP and Vimentin levels, inhibiting apoptotic pathway activation. It also leaded to an increase of Nestin and cyclin D1 expression levels. Conclusions Our results show that Aβ exposure on OECs induces an increase of TG2 levels and a different expression pattern of its isoforms and that Indicaxanthin pre-treatment stimulates OEC self-renewal through the reparative activity played by TG2. They also suggest that Aβ in OECs, both in the absence and in the presence of Indicaxanthin, might differently induce the transition of TG2 between “closed” and “open” conformation, providing a new mechanism involved in the signal pathways activated by the protein in Aβ injury important for neural regeneration of AD.

scholarly journals Amyloid-Beta induces different expression pattern of tissue transglutaminase and its isoforms on Olfactory Ensheathing Cells: modulatory effect of Indicaxanthin

2021 ◽  
Author(s):  
Agatina Campisi ◽  
Giuseppina Raciti ◽  
Giovanni Sposito ◽  
Rosaria Grasso ◽  
Maria A. Chiacchio ◽  
...  
Keyword(s):  
Superoxide Anion ◽  
Tissue Transglutaminase ◽  
Olfactory Ensheathing Cells ◽  
Glial Fibrillary Acid Protein ◽  
Cyclin D ◽  
Oxygen Species ◽  
Apoptotic Pathway ◽  
Pathway Activation ◽  
Acid Protein ◽  
Pre Treatment

Abstract Alzhèimer Disease (AD) is characterized by protein aggregates in the brain, including amyloid-beta (Aβ), a substrate for tissue transglutaminase (TG2). We assessed the effect of full native peptide of Aβ (1–42), the fragments (25–35 and 35–25) on TG2 expression and its isoforms (Long and Short) on mouse Olfactory Ensheathing Cells (OECs). The levels of cytoskeletal proteins, Vimentin and Glial Fibrillary Acid Protein, were also studied. The effect of the pre-treatment with Indicaxanthin on cell viability, total Reactive Oxygen Species, superoxide anion and apoptotic pathway activation was assessed. Since Nestin is co-expressed in pluripotent stem cells with cyclin D1, their levels were also evaluated. Our findings highlight that Aβ (1–42) and its fragments induced an increase of TG2 levels and the different expression pattern of its isoforms on OECs. Indicaxanthin pre-treatment was able to reduce TG2 over-expression upregulated by Aβ exposure of cells differently modulating its isoforms. In addition, it prevented total Reactive Oxygen Species and superoxide anion production, it reduced Glial Fibrillary Acid Protein and Vimentin levels and inhibited apoptotic pathway activation. It also leaded to an increase of Nestin and cyclin D1 expression, stimulating stem cells renewal through the reparative activity played by TG2. Our results suggest that Aβ in OECs, both in the absence and in the presence of Indicaxanthin, might differently induce the transition of TG2 between “closed” and “open” conformation, providing a new mechanism involved in the signal pathways activated by the protein in Aβ injury important for neural regeneration of AD.

Expression of tissue transglutaminase on primary olfactory ensheathing cells cultures exposed to stress conditions

2012 ◽  
Vol 72 (4) ◽  
pp. 289-295 ◽  
Author(s):  
Agata Campisi ◽  
Michela Spatuzza ◽  
Antonella Russo ◽  
Giuseppina Raciti ◽  
Angelo Vanella ◽  
...  
Keyword(s):  
Tissue Transglutaminase ◽  
Stress Conditions ◽  
Olfactory Ensheathing Cells ◽  
Ensheathing Cells

CDK 4/6 drug target activation mapping of HR+/HER2- metastatic breast cancer for treatment selection and response prediction.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13029-e13029
Author(s):  
Maysa M. Abu-Khalaf ◽  
Christos Hatzis ◽  
K. Alex Hodge ◽  
Frances Valdes ◽  
William M. Sikov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Metastatic Breast Cancer ◽  
Cyclin D1 ◽  
Expression Pattern ◽  
Drug Target ◽  
Metastatic Breast ◽  
Outcome Data ◽  
Biopsy Material ◽  
Pre Treatment

e13029 Background: Despite the fact that a number of CDK 4/6 inhibitors have become FDA approved as the main frontline therapy for HR+/HER2- metastatic breast cancer (MBC), there are no validated predictive markers of response to this class of drugs. Additionally, approximately 30-40% of patients (pts) have little to no response to these agents, with disease progression occurring in weeks to a few months after therapy initiation. We have initiated a clinical trial (NCT03195192) to utilize cutting edge proteomic technologies to map the functional activation of the signaling architecture of tumors taken from HR+/HER2- MBC pts at diagnosis. We plan to correlate these functional phosphoprotein-based signaling patterns with PFS intervals to identify candidate markers associated with response to CDK 4/6 inhibitor therapy. Methods: Pre-treatment diagnostic FFPE biopsy material from 26 individuals enrolled on study were analyzed by an LCM- reverse phase protein array workflow. Quantitative measurements of a focused set of 8 qualifying (pre-hypothesized) protein/phosphoprotein CDK 4/6 kinase pathway biomarkers, total Rb, Rb (S780), total Cyclin D1, Cyclin D1 (S286), total pI6INK, total p27, p27 (T187), FoxM1 (T600) were measured. Results: Baseline tumor tissue was successfully analyzed for 26 pts, 17 (65%) White, 8 (31%) African American, and 1 (4%) Asian; average age 62 (range 36-79); 4 pts (15%) had prior endocrine therapy and 4 (15 %) had chemotherapy in the adjuvant setting. Seven pts remain on study treatment. Unsupervised analysis revealed substantial concordance between a number of the total-phosphoprotein paired biomarkers, with 8/26 (31%) patients having relatively low activation/expression pattern (within the bottom quartile of the data range of the 8 markers) and 6/26 (23%) having relatively high activation/expression pattern within the top quartile of the data range of the 8 markers). Conclusions: Functional CDK 4/6 drug target pathway mapping analysis is possible from the pre-treatment diagnostic FFPE material and revealed sub-populations of patients who had systematically low and high levels of CDK 4/6 kinase substrate proteins and phosphoproteins that indicate overall drug target activity. Correlations of those patterns with PFS outcome data is ongoing with final analysis planned for Summer 2020. Clinical trial information: NCT03195192 .

Effect of Some Growth Factors on Tissue Transglutaminase Overexpression Induced by β-Amyloid in Olfactory Ensheathing Cells

2016 ◽  
Vol 54 (9) ◽  
pp. 6785-6794 ◽  
Author(s):  
Rosalia Pellitteri ◽  
Roberta Bonfanti ◽  
Michela Spatuzza ◽  
Maria Teresa Cambria ◽  
Mariacristina Ferrara ◽  
...  
Keyword(s):  
Growth Factors ◽  
Tissue Transglutaminase ◽  
Olfactory Ensheathing Cells ◽  
Ensheathing Cells ◽  
Β Amyloid

scholarly journals trans-Fatty acids promote p53-dependent apoptosis triggered by cisplatin-induced DNA interstrand crosslinks via the Nox-RIP1-ASK1-MAPK pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yusuke Hirata ◽  
Miki Takahashi ◽  
Yuto Yamada ◽  
Ryosuke Matsui ◽  
Aya Inoue ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Mapk Pathway ◽  
Regulatory Protein ◽  
Strand Break ◽  
Mitogen Activated Protein Kinase ◽  
Ros Generation ◽  
Apoptotic Pathway ◽  
Interstrand Crosslinks ◽  
Pathway Activation ◽  
Dna Interstrand Crosslinks

Abstracttrans-Fatty acids (TFAs) are food-derived fatty acids associated with various diseases including cardiovascular diseases. However, the underlying etiology is poorly understood. Here, we show a pro-apoptotic mechanism of TFAs such as elaidic acid (EA), in response to DNA interstrand crosslinks (ICLs) induced by cisplatin (CDDP). We previously reported that TFAs promote apoptosis induced by doxorubicin (Dox), a double strand break (DSB)-inducing agent, via a non-canonical apoptotic pathway independent of tumor suppressor p53 and apoptosis signal-regulating kinase (ASK1), a reactive oxygen species (ROS)-responsive kinase. However, here we found that in the case of CDDP-induced apoptosis, EA-mediated pro-apoptotic action was reversed by knockout of either p53 or ASK1, despite no increase in p53 apoptotic activity. Upon CDDP treatment, EA predominantly enhanced ROS generation, ASK1-p38/c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathway activation, and ultimately cell death, all of which were suppressed either by co-treatment of the NADPH oxidase (Nox) inhibitor Apocynin, or by knocking out its regulatory protein, receptor-interacting protein 1 (RIP1). These results demonstrate that in response to CDDP ICLs, TFAs promote p53-dependent apoptosis through the enhancement of the Nox-RIP1-ASK1-MAPK pathway activation, providing insight into the diverse pathogenetic mechanisms of TFAs according to the types of DNA damage.

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