Cellular Processes Involved in Jurkat Cells Exposed to Nanosecond Pulsed Electric Field

Abstract

Recently, nanosecond pulsed electric field (nsPEF) has been considered as a new tool for tumor therapy, but its molecular mechanism of function remains to be fully elucidated. Here, we explored the cellular processes of Jurkat cells exposed to nanosecond pulsed electric field. Differentially expressed genes (DEGs) were acquired from the GEO2R, followed by analysis with a series of bioinformatics tools. Subsequently, 3D protein models of hub genes were modeled by Modeller 9.21 and Rosetta 3.9. Then, a 100 ns molecular dynamics simulation for each hub protein was performed with GROMACS 2018.2. Finally, three kinds of nsPEF voltages (0.01, 0.05, and 0.5 mV/mm) were used to simulate the molecular dynamics of hub proteins for 100 ns. A total of 1769 DEGs and eight hub genes were obtained. Molecular dynamic analysis, including root mean square deviation (RMSD), root mean square fluctuation (RMSF), and the Rg, demonstrated that the 3D structure of hub proteins was built, and the structural characteristics of hub proteins under different nsPEFs were acquired. In conclusion, we explored the effect of nsPEF on Jurkat cell signaling pathway from the perspective of molecular informatics, which will be helpful in understanding the complex effects of nsPEF on acute T-cell leukemia Jurkat cells.

Nanosecond Pulsed Electric Field Only Transiently Affects the Cellular and Molecular Processes of Leydig Cells

“…Overexpression of genes coding for membrane-associated proteins in nsPEF-exposed cells, even if different for individual proteins, was consistent with other studies [ 28 , 79 ]. The downregulation of genes involved in the cell cycle and DNA repair was also previously identified in Jurkat cells following nsPEF treatment [ 77 ]. Nevertheless, the magnitude of changes seemed to be higher in the immune cells since significant differential expression could be detected for individual genes.…”

“…Other noteworthy time-related changes included a high overexpression of Fos (FBJ osteosarcoma oncogene), Jun (jun proto-oncogene), and Egr1 (early growth response 1) immediately after nsPEF, both in the sham- and nsPEF-exposed cells. This finding was surprising because previous works strongly associated increased expression of these genes with nsPEF treatment in Jurkat cells and fibroblasts [ 77 , 78 , 79 , 81 ]. Fos , Jun, and Egr1 are well-characterized immediate-early response genes whose transcription is activated within minutes after stimulation with extracellular or intracellular cues (e.g., cytokines, growth factors, shear stress, or UV damage) [ 82 , 83 , 84 ].…”

“…Transcriptome analysis, in our study, had the unique property of including the immediate, early (4 h), and late response (24 h) of cells to nsPEF exposure, in contrast to previously published studies analysing the differential gene expression of the immediate (at 0.5 and 1 h) [ 77 ] and early (at 4 h) cell responses [ 78 , 79 ]. This allowed us to trace the nsPEF-related variations in gene expression for the first time over a more extended period.…”

“…For example, the negative enrichment of genes involved in DNA repair was most prominent at 4 h after nsPEF exposure, whereas after 24 h, the overall expression levels of genes in this set in nsPEF-exposed cells were more comparable to the sham samples. The genes in nsPEF-exposed Jurkat cells were also transiently overexpressed; the differential expression of the genes involved in biochemical pathways was most prominent 30 min after treatment, whereas, at 60 min, the cell cycle and gene transcription pathways were the most affected processes after nsPEF treatment [ 77 ]. On a smaller scale, an initial overexpression due to nsPEF exposure, followed by a drop in protein levels up to 12 h after exposure, were also observed for proteins involved in the MAPK signalling pathway in Jurkat and U937 cells [ 79 ].…”

Artificial Neural Network Analysis of Geo Database in Diagnosing Papillary Thyroid Carcinoma

“…As the most important basis for formulating treatment plans, it is possible to decide whether or not to operate, and the postoperative of chemotherapy [35], some are even effective drugs that can accurately determine malignant tumors [36]. Among evidences, with the development of gene chip technology [37], the information provided by individual gene chip results has been paid more and more attention, and it can even be referred to together with the results of imaging or laboratory science in recent years [38].…”