title: Down regulation of N-acetylglucosaminyltransferase V facilitates all-transretinoic acid to induce apoptosis of human hepatocarcinoma cells.
abstract: After N-acetylglucosaminyltransferase V (GnT-V) activity was down-regulated by the transfection of its antisense cDNA(GnTV-AS), apoptosis of H7721 cells was appeared and the apoptosis induced by 80 microM all-transretinoic acid (ATRA) was facilitated, while ATRA itself could not induce apparent apoptosis in mock cells transfected with the vector. In the study of the molecular mechanism of this phenomenon, it was found that GnTV-AS reduced the expressions of anti-apoptotic proteins, such as phosphorylated protein kinase B and phosphorylated Bad as well as Bcl-2 and Bcl-X (L), and elevated those of pro-apoptotic proteins, including Bax, full length caspase-3 and its activated fragments as well as anti-oncoprotein p53. In the contrast, ATRA up regulated the expressions of Bax and activated caspase-3 fragments only. After the GnTV-AS transfected cells were treated with ATRA, phosphorylated PKB and Bad were further decreased, while Bax and activated caspase-3 fragment were further increased, leading to the enhanced apoptosis in flow-cytometry analysis when compared with GnTV-AS cells not treated with ATRA. It was speculated that the decreased phospho-Bad resulted from the reduced phospho-PKB and the up regulation of p53 caused the elevated activity of Bax. The increased active caspase-3 was the consequence of the elevated Bax/ Bcl-2(Bcl-X(L)) activity ratio in the cells.
authors.affiliation: Key Laboratory of Glycoconjugate Research, Ministry of Health, Department of Biochemistry, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.forename: Hai-jiao
authors.initials: HJ
authors.lastname: Chen
authors.forename: Qiu-yan
authors.initials: QY
authors.lastname: Wang
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis* / Q000235:genetics; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494819:BAD protein, human; C494826:BAX protein, human; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D000072000:NF-KappaB Inhibitor alpha; D014212:Tretinoin; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; D051057:Proto-Oncogene Proteins c-akt; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases