DMA, a bisbenzimidazole, offers radioprotection by promoting NFκB transactivation through NIK/IKK in human glioma cells.

<h4>Background</h4>Ionizing radiation (IR) exposure often occurs for human beings through occupational, medical, environmental, accidental and/or other sources. Thus, the role of radioprotector is essential to overcome the complex series of overlapping responses to radiation induced DNA...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Navrinder Kaur, Atul Ranjan, Vinod Tiwari, Ritu Aneja, Vibha Tandon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4aa79dd3332b4b1392cc3d08cd9488fe
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4aa79dd3332b4b1392cc3d08cd9488fe
record_format	dspace
spelling	oai:doaj.org-article:4aa79dd3332b4b1392cc3d08cd9488fe2021-11-18T07:14:40ZDMA, a bisbenzimidazole, offers radioprotection by promoting NFκB transactivation through NIK/IKK in human glioma cells.1932-620310.1371/journal.pone.0039426https://doaj.org/article/4aa79dd3332b4b1392cc3d08cd9488fe2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22745752/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Ionizing radiation (IR) exposure often occurs for human beings through occupational, medical, environmental, accidental and/or other sources. Thus, the role of radioprotector is essential to overcome the complex series of overlapping responses to radiation induced DNA damage.<h4>Methods and results</h4>Treatment of human glioma U87 cells with DMA (5- {4-methylpiperazin-1-yl}-2-[2'-(3, 4-dimethoxyphenyl)-5'-benzimidazolyl] in the presence or absence of radiation uncovered differential regulation of an array of genes and proteins using microarray and 2D PAGE techniques. Pathway construction followed by relative quantitation of gene expression of the identified proteins and their interacting partners led to the identification of MAP3K14 (NFκB inducing kinase, NIK) as the candidate gene affected in response to DMA. Subsequently, over expression and knock down of NIK suggested that DMA affects NFκB inducing kinase mediated phosphorylation of IKKα and IKKβ both alone and in the presence of ionizing radiation (IR). The TNF-α induced NFκB dependent luciferase reporter assay demonstrated 1.65, 2.26 and 3.62 fold increase in NFκB activation at 10, 25 and 50 µM DMA concentrations respectively, compared to control cells. This activation was further increased by 5.8 fold in drug + radiation (50 µM +8.5 Gy) treated cells in comparison to control. We observed 51% radioprotection in control siRNA transfected cells that attenuated to 15% in siRNA NIK treated U87 cells, irradiated in presence of DMA at 24 h.<h4>Conclusions</h4>Our studies show that NIK/IKK mediated NFκB activation is more intensified in cells over expressing NIK and treated with DMA, alone or in combination with ionizing radiation, indicating that DMA promotes NIK mediated NFκB signaling. This subsequently leads to the radioprotective effect exhibited by DMA.Navrinder KaurAtul RanjanVinod TiwariRitu AnejaVibha TandonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39426 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Navrinder Kaur Atul Ranjan Vinod Tiwari Ritu Aneja Vibha Tandon DMA, a bisbenzimidazole, offers radioprotection by promoting NFκB transactivation through NIK/IKK in human glioma cells.
description	<h4>Background</h4>Ionizing radiation (IR) exposure often occurs for human beings through occupational, medical, environmental, accidental and/or other sources. Thus, the role of radioprotector is essential to overcome the complex series of overlapping responses to radiation induced DNA damage.<h4>Methods and results</h4>Treatment of human glioma U87 cells with DMA (5- {4-methylpiperazin-1-yl}-2-[2'-(3, 4-dimethoxyphenyl)-5'-benzimidazolyl] in the presence or absence of radiation uncovered differential regulation of an array of genes and proteins using microarray and 2D PAGE techniques. Pathway construction followed by relative quantitation of gene expression of the identified proteins and their interacting partners led to the identification of MAP3K14 (NFκB inducing kinase, NIK) as the candidate gene affected in response to DMA. Subsequently, over expression and knock down of NIK suggested that DMA affects NFκB inducing kinase mediated phosphorylation of IKKα and IKKβ both alone and in the presence of ionizing radiation (IR). The TNF-α induced NFκB dependent luciferase reporter assay demonstrated 1.65, 2.26 and 3.62 fold increase in NFκB activation at 10, 25 and 50 µM DMA concentrations respectively, compared to control cells. This activation was further increased by 5.8 fold in drug + radiation (50 µM +8.5 Gy) treated cells in comparison to control. We observed 51% radioprotection in control siRNA transfected cells that attenuated to 15% in siRNA NIK treated U87 cells, irradiated in presence of DMA at 24 h.<h4>Conclusions</h4>Our studies show that NIK/IKK mediated NFκB activation is more intensified in cells over expressing NIK and treated with DMA, alone or in combination with ionizing radiation, indicating that DMA promotes NIK mediated NFκB signaling. This subsequently leads to the radioprotective effect exhibited by DMA.
format	article
author	Navrinder Kaur Atul Ranjan Vinod Tiwari Ritu Aneja Vibha Tandon
author_facet	Navrinder Kaur Atul Ranjan Vinod Tiwari Ritu Aneja Vibha Tandon
author_sort	Navrinder Kaur
title	DMA, a bisbenzimidazole, offers radioprotection by promoting NFκB transactivation through NIK/IKK in human glioma cells.
title_short	DMA, a bisbenzimidazole, offers radioprotection by promoting NFκB transactivation through NIK/IKK in human glioma cells.
title_full	DMA, a bisbenzimidazole, offers radioprotection by promoting NFκB transactivation through NIK/IKK in human glioma cells.
title_fullStr	DMA, a bisbenzimidazole, offers radioprotection by promoting NFκB transactivation through NIK/IKK in human glioma cells.
title_full_unstemmed	DMA, a bisbenzimidazole, offers radioprotection by promoting NFκB transactivation through NIK/IKK in human glioma cells.
title_sort	dma, a bisbenzimidazole, offers radioprotection by promoting nfκb transactivation through nik/ikk in human glioma cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/4aa79dd3332b4b1392cc3d08cd9488fe
work_keys_str_mv	AT navrinderkaur dmaabisbenzimidazoleoffersradioprotectionbypromotingnfkbtransactivationthroughnikikkinhumangliomacells AT atulranjan dmaabisbenzimidazoleoffersradioprotectionbypromotingnfkbtransactivationthroughnikikkinhumangliomacells AT vinodtiwari dmaabisbenzimidazoleoffersradioprotectionbypromotingnfkbtransactivationthroughnikikkinhumangliomacells AT rituaneja dmaabisbenzimidazoleoffersradioprotectionbypromotingnfkbtransactivationthroughnikikkinhumangliomacells AT vibhatandon dmaabisbenzimidazoleoffersradioprotectionbypromotingnfkbtransactivationthroughnikikkinhumangliomacells
_version_	1718423723566956544

DMA, a bisbenzimidazole, offers radioprotection by promoting NFκB transactivation through NIK/IKK in human glioma cells.

Ejemplares similares