Hsp70 chaperone rescues C6 rat glioblastoma cells from oxidative stress by sequestration of aggregating GAPDH.

作者: Vladimir F. Lazarev , Alina D. Nikotina , Elena R. Mikhaylova , Evgeny Nudler , Sergey G. Polonik

DOI: 10.1016/J.BBRC.2015.12.076

关键词:

摘要: The Hsp70 chaperone is known to elicit cytoprotective activity and this protection has a negative impact in anti-tumor therapy. In cancer cells subjected oxidative stress may bind damaged polypeptides proteins involved apoptosis signaling. Since one of the important targets glyceraldehyde-3-phospate dehydrogenase (GAPDH) we suggested that might its protective effect by binding GAPDH. Microscopy data show C6 rat glioma hydrogen peroxide treatment considerable proportion GAPDH molecules are denatured according dot ultrafiltration they form SDS-insoluble aggregates. Using two newly developed assays can oxidized an ATP-dependent manner. Pharmacological up- or down-regulation with aid U133 echinochrome triptolide, respectively, reduced increased number containing aggregates dying due peroxide. immunoprecipitation found able sequester aggregation-prone explain anti-oxidative power chaperone. results study led us conclude constantly exposed conditions stress, should be abolished specific inhibitors expression.

参考文章(27)
Maxim A. Shevtsov, Elena Y. Komarova, Darya A. Meshalkina, Natalia V. Bychkova, Nikolai D. Aksenov, Sergey V. Abkin, Boris A. Margulis, Irina V. Guzhova, Exogenously delivered heat shock protein 70 displaces its endogenous analogue and sensitizes cancer cells to lymphocytes-mediated cytotoxicity. Oncotarget. ,vol. 5, pp. 3101- 3114 ,(2014) , 10.18632/ONCOTARGET.1820
Masanori Itakura, Hidemitsu Nakajima, Yuko Semi, Shusaku Higashida, Yasu-Taka Azuma, Tadayoshi Takeuchi, Glyceraldehyde-3-phosphate dehydrogenase aggregation inhibitor peptide: A potential therapeutic strategy against oxidative stress-induced cell death Biochemical and Biophysical Research Communications. ,vol. 467, pp. 373- 376 ,(2015) , 10.1016/J.BBRC.2015.09.150
Vladimir F. Lazarev, Konstantin A. Benken, Pavel I. Semenyuk, Svetlana V. Sarantseva, Olga I. Bolshakova, Elena R. Mikhaylova, Vladimir I. Muronetz, Irina V. Guzhova, Boris A. Margulis, GAPDH binders as potential drugs for the therapy of polyglutamine diseases: Design of a new screening assay FEBS Letters. ,vol. 589, pp. 581- 587 ,(2015) , 10.1016/J.FEBSLET.2015.01.018
V. F. Lazarev, K. V. Onokhin, O. I. Antimonova, S. G. Polonik, I. V. Guzhova, B. A. Margulis, Kinetics of chaperone activity of proteins Hsp70 and Hdj1 in human leukemia U-937 cells after preconditioning with thermal shock or compound U-133 Biochemistry. ,vol. 76, pp. 590- 595 ,(2011) , 10.1134/S0006297911050099
Irina V. Guzhova, Maxim A. Shevtsov, Sergey V. Abkin, Katerina M. Pankratova, Boris A. Margulis, Intracellular and extracellular Hsp70 chaperone as a target for cancer therapy. International Journal of Hyperthermia. ,vol. 29, pp. 399- 408 ,(2013) , 10.3109/02656736.2013.807439
M Y Sherman, V L Gabai, Hsp70 in cancer: back to the future Oncogene. ,vol. 34, pp. 4153- 4161 ,(2015) , 10.1038/ONC.2014.349
Anne-Laure Joly, Guillaume Wettstein, Gregoire Mignot, François Ghiringhelli, Carmen Garrido, Dual role of heat shock proteins as regulators of apoptosis and innate immunity. Journal of Innate Immunity. ,vol. 2, pp. 238- 247 ,(2010) , 10.1159/000296508
Hidemitsu Nakajima, Wataru Amano, Takeya Kubo, Ayano Fukuhara, Hideshi Ihara, Yasu-Taka Azuma, Hisao Tajima, Takashi Inui, Akira Sawa, Tadayoshi Takeuchi, Glyceraldehyde-3-phosphate Dehydrogenase Aggregate Formation Participates in Oxidative Stress-induced Cell Death Journal of Biological Chemistry. ,vol. 284, pp. 34331- 34341 ,(2009) , 10.1074/JBC.M109.027698
Jose Pedro Castro, Christiane Ott, Tobias Jung, Tilman Grune, Henrique Almeida, Carbonylation of the cytoskeletal protein actin leads to aggregate formation Free Radical Biology and Medicine. ,vol. 53, pp. 916- 925 ,(2012) , 10.1016/J.FREERADBIOMED.2012.06.005
Rehana K. Leak, Heat shock proteins in neurodegenerative disorders and aging. Journal of Cell Communication and Signaling. ,vol. 8, pp. 293- 310 ,(2014) , 10.1007/S12079-014-0243-9