Geldanamycin-Induced Phosphatidylserine Translocation in the Erythrocyte Membrane

作者: Kashif Jilani , Syed M. Qadri , Florian Lang

DOI: 10.1159/000356596

关键词: AnnexinBiophysicsGeldanamycinExtracellularPhosphatidylserineCell biologyBiologyCell membraneCeramideCytosolApoptosis

摘要: Background/aims: Geldanamycin, a benzoquinone ansamycin antibiotic, and its analogues induce apoptosis of tumor cells are thus considered for the treatment cancer. Similar to nucleated cells, erythrocytes may enter eryptosis, suicidal erythrocyte death characterized by cell shrinkage membrane scrambling with phosphatidylserine-exposure at surface. Triggers eryptosis include increase cytosolic Ca2+-concentration ([Ca2+]i) formation ceramide. The present study explored, whether geldanamycin modifies [Ca2+]i, ceramide formation, volume phosphatidylserine abundance Methods: Erythrocyte was estimated from forward scatter, phosphatidylserine-abundance annexin V binding, hemolysis hemoglobin release, binding fluorescent antibodies [Ca2+]i Fluo3-fluorescence. Results: A 48 hours exposure significantly decreased scatter (≥ 5 µM), increased annexin-V-binding 25 but did not modify Fluo3-fluorescence (up 50 µM). following modified removal extracellular Ca2+ paralleled (50 Conclusions: Geldanamycin stinulated an effect least partially due formation.

参考文章(93)
Wei-Wei Chen, Hailong Yu, Hong-Bin Fan, Cui-Cui Zhang, Min Zhang, Caiyi Zhang, Yanbo Cheng, Jiming Kong, Chun-Feng Liu, Deqin Geng, Xingshun Xu, RIP1 mediates the protection of geldanamycin on neuronal injury induced by oxygen-glucose deprivation combined with zVAD in primary cortical neurons. Journal of Neurochemistry. ,vol. 120, pp. 70- 77 ,(2012) , 10.1111/J.1471-4159.2011.07526.X
Nazneen Shaik, Mohanad Zbidah, Florian Lang, Inhibition of Ca(2+) entry and suicidal erythrocyte death by naringin. Cellular Physiology and Biochemistry. ,vol. 30, pp. 678- 686 ,(2012) , 10.1159/000341448
Evelyn Böttger, Gabriele Multhoff, Jürgen F. J. Kun, Meral Esen, Plasmodium falciparum-Infected Erythrocytes Induce Granzyme B by NK Cells through Expression of Host-Hsp70 PLoS ONE. ,vol. 7, pp. e33774- ,(2012) , 10.1371/JOURNAL.PONE.0033774
Jeffrey G. Supko, Robert L. Hickman, Michael R. Grever, Louis Malspeis, Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. Cancer Chemotherapy and Pharmacology. ,vol. 36, pp. 305- 315 ,(1995) , 10.1007/BF00689048
Justin R. Pritchard, Benjamin D. Cosgrove, Michael T. Hemann, Linda G. Griffith, Jack R. Wands, Douglas A. Lauffenburger, Three-kinase inhibitor combination recreates multipathway effects of a geldanamycin analogue on hepatocellular carcinoma cell death Molecular Cancer Therapeutics. ,vol. 8, pp. 2183- 2192 ,(2009) , 10.1158/1535-7163.MCT-08-1203
Pengrong Yan, Guoliang Qing, Zhaoxia Qu, Chang-Chih Wu, Arnold Rabson, Gutian Xiao, Targeting Autophagic Regulation of NF-kappaB in HTLV-I Transformed Cells by Geldanamycin: Implications for Therapeutic Interventions Autophagy. ,vol. 3, pp. 600- 603 ,(2007) , 10.4161/AUTO.4761
Daiana M. Vota, Romina E. Maltaneri, Shirley D. Wenker, Alcira B. Nesse, Daniela C. Vittori, Differential Erythropoietin Action upon Cells Induced to Eryptosis by Different Agents Cell Biochemistry and Biophysics. ,vol. 65, pp. 145- 157 ,(2013) , 10.1007/S12013-012-9408-4
C Brugnara, L de Franceschi, S L Alper, Inhibition of Ca(2+)-dependent K+ transport and cell dehydration in sickle erythrocytes by clotrimazole and other imidazole derivatives. Journal of Clinical Investigation. ,vol. 92, pp. 520- 526 ,(1993) , 10.1172/JCI116597
Irene P Lau, Huanjun Chen, Jianfang Wang, Hock C Ong, Ken C-F Leung, Ho P Ho, Siu K Kong, None, In vitro effect of CTAB- and PEG-coated gold nanorods on the induction of eryptosis/erythroptosis in human erythrocytes. Nanotoxicology. ,vol. 6, pp. 847- 856 ,(2012) , 10.3109/17435390.2011.625132