Publications by authors named "M Thangaraj"

29 Publications

Immunoediting role for major vault protein in apoptotic signaling induced by bacterial -acyl homoserine lactones.

Proc Natl Acad Sci U S A 2021 Mar;118(12)

Department of Chemistry and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Be'er Sheva 8410501, Israel;

The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses to Here, we report the use of photoactive probes to identify MVP as a target of the -(3-oxo-dodecanoyl) homoserine lactone (C12), a quorum sensing signal of certain proteobacteria including A treatment of normal and cancer cells with C12 or other -acyl homoserine lactones (AHLs) results in rapid translocation of MVP into lipid raft (LR) membrane fractions. Like AHLs, inflammatory stimuli also induce LR-localization of MVP, but the C12 stimulation reprograms (functionalizes) bioactivity of the plasma membrane by recruiting death receptors, their apoptotic adaptors, and caspase-8 into LR. These functionalized membranes control AHL-induced signaling processes, in that MVP adjusts the protein kinase p38 pathway to attenuate programmed cell death. Since MVP is the structural core of large particles termed vaults, our findings suggest a mechanism in which MVP vaults act as sentinels that fine-tune inflammation-activated processes such as apoptotic signaling mediated by immunosurveillance cytokines including tumor necrosis factor-related apoptosis inducing ligand (TRAIL).
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http://dx.doi.org/10.1073/pnas.2012529118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000436PMC
March 2021

Immunological and antibiofilm property of haemocyanin purified from grooved tiger shrimp (Penaeus semisulcatus): An in vitro and in silico approach.

Microb Pathog 2020 Oct 25;147:104253. Epub 2020 Jun 25.

Crustacean Molecular Biology and Genomics Division, Biomaterials and Biotechnology in Animal Health Lab, Department of Animal Health and Management, Alagappa University, Karaikudi, 630 004, Tamil Nadu, India. Electronic address:

Haemocyanin (Hc) is a non-specific innate immune protein present in the haemolymph of arthropods and molluscs. In the current study, we characterized the structural and immunological properties of Hc from grooved tiger shrimp, Penaeus semisulcatus. Hc was isolated from the haemolymph of P. semisulcatus by gel filtration column chromatography using Sephadex G-100. High-performance liquid chromatography of the purified Hc emerged as a single peak through a retention time of 3.3 min demonstrating the homogeneity nature of the protein. X-ray diffraction analysis revealed a distinct peak at 31.7° indicating the crystalline character of the purified Hc. Circular dichroism spectra of the purified Hc displayed negative ellipticity bands close to 225 nm and 208 nm representing β-sheet secondary structure. The purified Hc agglutinated sheep RBCs, yeast Saccharomyces cerevisiae and fungal Candida albicans. In addition, the purified Hc displayed antibacterial activity against Gram-positive bacteria (Bacillus thuringiensis and Bacillus pumilis) and Gram-negative bacteria (Vibrio parahaemolyticus and Vibrio alginolyticus) with a minimal inhibitory concentration of 50 μg/ml. Antibiofilm activity revealed the potential of purified Hc to inhibit biofilm formation of both Gram-positive and Gram-negative bacterial pathogens. Furthermore, live/dead staining of biofilms demonstrated the reduced viability of bacterial cells after exposure to the purified Hc. In silico molecular modeling was carried out using the sequence of Hc from SwissProt and molecular docking was performed with the cell surface components found in Gram-positive and Gram-negative bacteria. Overall our study demonstrates the involvement of Hc in the native immune reaction of P. semisulcatus by eliciting pathogen recognition. Thus, Hc could enhance disease resistance against pathogenic infection in shrimp aquaculture.
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http://dx.doi.org/10.1016/j.micpath.2020.104253DOI Listing
October 2020

Enhancing the Surface Quality of Micro Titanium Alloy Specimen in WEDM Process by Adopting TGRA-Based Optimization.

Materials (Basel) 2020 Mar 21;13(6). Epub 2020 Mar 21.

Department of Oral and Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia.

The surface measures of machined titanium alloys as dental materials can be enhanced by adopting a decision-making algorithm in the machining process. The surface quality is normally characterized by more than one quality parameter. Hence, it is very important to establish multi-criteria decision making to compute the optimal process factors. In the present study, Taguchi-Grey analysis-based criteria decision making has been applied to the input process factors in the wire EDM (electric discharge machining) process. The recast layer thickness, wire wear ratio and micro hardness have been chosen to evaluate the quality measures. It was found that the wire electrode selection was the most influential factor on the quality measures in the WEDM process, due to its significance in creating spark energy. The optimal arrangement of the input process parameters has been found using the proposed approach as gap voltage (70 V), discharge current (15 A) and duty factor (0.6). It was proved that the proposed method can enhance the efficacy of the process. Utilizing the computed combination of optimal process parameters in surface quality analysis has significantly contributed to improving the quality of machining surface.
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http://dx.doi.org/10.3390/ma13061440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143623PMC
March 2020

Htra1 is a Novel Transcriptional Target of RUNX2 That Promotes Osteogenic Differentiation.

Cell Physiol Biochem 2019 ;53(5):832-850

Laboratory of Molecular Cell Biology, College of Pharmacy and Nutrition and Neuroscience Research Cluster, University of Saskatchewan, Saskatoon, SK, Canada.

Background/aims: Runt-related transcription factor 2 (Runx2) is a master regulator of osteogenic differentiation, but most of the direct downstream targets of RUNX2 during osteogenesis are unknown. Likewise, High-temperature requirement factor A1 (HTRA1) is a serine protease expressed in bone, yet the role of Htra1 during osteoblast differentiation remains elusive. We investigated the role of Htra1 in osteogenic differentiation and the transcriptional regulation of Htra1 by RUNX2 in primary mouse mesenchymal progenitor cells.

Methods: Overexpression of Htra1 was carried out in primary mouse mesenchymal progenitor cells to evaluate the extent of osteoblast differentiation. Streptavidin agarose pulldown assay, chromatin immunoprecipitation assay, and dual luciferase assay were carried out to investigate the interaction of RUNX2 protein at the Htra1 promoter during osteoblast differentiation.

Results: Overexpression of Htra1 increased the production of mineralized bone matrix, upregulating several osteoblast genes, such as Sp7 transcription factor (Sp7) and Alkaline phosphatase, liver/bone/kidney (Alpl). In addition, Htra1 upregulated osteogenesis-related signalling genes, such as Fibroblast growth factor 9 (Fgf9) and Vascular endothelial growth factor A (Vegfa). A series of experiments confirmed Htra1 as a direct RUNX2 transcriptional target. Overexpression of Runx2 resulted in the upregulation of Htra1 mRNA and protein. Chromatin immunoprecipitation and streptavidin agarose pull-down assays showed that RUNX2 binds a proximal -400 bp region of the Htra1 promoter during osteogenic differentiation. Dual luciferase assays confirmed that RUNX2 activates the proximal Htra1 promoter during osteogenic differentiation. Mutation of putative RUNX2 binding sites revealed that RUNX2 interacts with the Htra1 promoter at -252 bp and -84 bp to induce Htra1 expression.

Conclusion: We demonstrate that Htra1 is a positive regulator of osteogenic differentiation, showing for the first time that Htra1 is a direct downstream target of RUNX2.
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http://dx.doi.org/10.33594/000000176DOI Listing
November 2019

Sirt2 epigenetically down-regulates PDGFRα expression and promotes CG4 cell differentiation.

Cell Cycle 2019 05 10;18(10):1095-1109. Epub 2019 May 10.

a Department of Biochemistry and Molecular Biology , Basic Medical School, Henan University , Kaifeng , China.

We have previously found that Sirt2 enhanced the outgrowth of cellular processes and MBP expression in CG4 cells, where Sirt2 expression is suppressed by transcription factor Nkx2.2. However, the detailed mechanism of Sirt2 facilitating oligodendroglial cell differentiation remained unclear. In the present study, we observed that Sirt2 partially translocated into the nuclei when CG4 cells were induced to differentiate. Sirt2 was detected at the CpG island of PDGFRα promoter via ChIP assay during the cells differentiation process rather than during the state of growth. Sirt2 deacetylated protein(s) bound to the promoter of PDGFRα and simultaneously appeared to facilitate histone3 K27 tri-methylation, both of which are suppressive signatures on gene transcription activation. In bisulfate assay, we identified that Sirt2 significantly induced DNA methylation of PDGFRα promoter compared with the control. Consistently, Sirt2 overexpression down-regulated PDGFRα expression in CG4 cells. The knock-down of PDGFRα or Sirt2 over-expression repressed cell proliferation, but knock-down of Sirt2 promoted cell proliferation. Taken together, Sirt2 translocated into the nuclei while the cells initiated a differentiation process, facilitating CG4 cell differentiation partially through epigenetic modification and suppression of PDGFRα expression. The repression of PDGFRα expression mediated by Sirt2 appeared to facilitate a transition of cellular processes, i.e. from a proliferating progenitor state to a post-mitotic state in CG4 cells.
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http://dx.doi.org/10.1080/15384101.2019.1609818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592232PMC
May 2019
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