caa a22 4500 606234160 CHVBK 20210128101235.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s11010-014-2237-6 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2237-6 TGF-β-induced hCG-β regulates redox homeostasis in glioma cells [Elektronische Daten] [Fahim Ahmad, Sadashib Ghosh, Sanchari Sinha, Shanker Joshi, Veer Mehta, Ellora Sen] Transforming growth factor (TGF-β) is associated with the progression of glioblastoma multiforme (GBM)—the most malignant of brain tumors. Since there is a structural homology between TGF-β and human chorionic gonadotropin (hCG) and as both TGF-β and hCG-β are known regulators of oxidative stress and survival responses in a variety of tumors, the role of TGF-β in the regulation of hCG-β and its consequences on redox modulation of glioblastoma cells was investigated. A heightened hCG-β level was observed in GBM tumors. TGF-β treatment increased hCG-β expression in glioma cell lines, and this heightened hCG-β was found to regulate redox homeostasis in TGF-β-treated glioma cells, as siRNA-mediated knockdown of hCG-β (i) elevated reactive oxygen species (ROS) generation, (ii) decreased thioredoxin Trx1 expression and thioredoxin reductase (TrxR) activity, and (iii) abrogated expression of TP53-induced glycolysis and apoptosis regulator (TIGAR). Silencing of hCG-β abrogated Smad2/3 levels, suggesting the existence of TGF-β-hCG-β cross-talk in glioma cells. siRNA-mediated inhibition of elevated TIGAR levels in TGF-β-treated glioma cells was accompanied by an increase in ROS levels. As a farnesyltransferase inhibitor, Manumycin is known to induce glioma cell apoptosis in a ROS-dependent manner, and we investigated whether Manumycin could induce apoptosis in TGF-β-treated cells with elevated hCG-β exhibiting ROS-scavenging property. Manumycin-induced apoptosis in TGF-β-treated cells was accompanied by elevated ROS levels and decreased expression of hCG-β, Trx1, Smad2/3, and TIGAR. These findings indicate the existence of a previously unknown TGF-β-hCG-β link that regulates redox homeostasis in glioma cells. Springer Science+Business Media New York, 2014 TGF nationallicence hCG nationallicence ROS nationallicence TIGAR nationallicence Ahmad Fahim National Brain Research Centre, 122 051, Manesar, Haryana, India aut Ghosh Sadashib National Brain Research Centre, 122 051, Manesar, Haryana, India aut Sinha Sanchari National Brain Research Centre, 122 051, Manesar, Haryana, India aut Joshi Shanker National Brain Research Centre, 122 051, Manesar, Haryana, India aut Mehta Veer Paras Hospitals, Gurgaon, India aut Sen Ellora National Brain Research Centre, 122 051, Manesar, Haryana, India aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 399/1-2(2015-01-01), 105-112 0300-8177 399:1-2<105 2015 399 11010 https://doi.org/10.1007/s11010-014-2237-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2237-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ahmad Fahim National Brain Research Centre, 122 051, Manesar, Haryana, India aut NATIONALLICENCE 700 1- Ghosh Sadashib National Brain Research Centre, 122 051, Manesar, Haryana, India aut NATIONALLICENCE 700 1- Sinha Sanchari National Brain Research Centre, 122 051, Manesar, Haryana, India aut NATIONALLICENCE 700 1- Joshi Shanker National Brain Research Centre, 122 051, Manesar, Haryana, India aut NATIONALLICENCE 700 1- Mehta Veer Paras Hospitals, Gurgaon, India aut NATIONALLICENCE 700 1- Sen Ellora National Brain Research Centre, 122 051, Manesar, Haryana, India aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 399/1-2(2015-01-01), 105-112 0300-8177 399:1-2<105 2015 399 11010