Apoptosis caused by Hsp90 inhibitor geldanamycin in Leishmania donovani during promastigote-to-amastigote transformation stage.
The role of heat shock protein 90 inhibitor geldanamycin (GA) during Leishmania donovani promastigote-to-amastigote transformation in axenic conditions was investigated. Promastigotes exhibited apoptotic morphologic changes after GA treatment at a high temperature, and the effect is in a dose- and time-dependant manner. Meanwhile, cell cycle analysis showed a significant increase at the expense of cells in the G0/G1 phase and a decrease in the S and G2/M phases after GA treatment. In addition, cellular glutathione level was reduced and reactive oxygen species content was increased afterwards. Pretreatment with antioxidants reduced the percentage of GA-induced cell apoptosis. After treatment, cultures in pH 5.5 showed a lower percentage of apoptosis than those in pH 7.4. The present study showed that GA could cause apoptosis in L. donovani but could not cause stage differentiation in high temperature and that acidic conditions were likely to be crucial for the transformation and survival of the parasite within its human host.
Li
Qiaoli
Q
Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China.
Zhou
Ying
Y
Yao
Chenjiang
C
Ma
Xiaoping
X
Wang
Lianyun
L
Xu
Wangjie
W
Wang
Zhaoxia
Z
Qiao
Zhongdong
Z
D000818:Animals; D000975:Antioxidants; D017209:Apoptosis; D016227:Benzoquinones / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000032:analysis; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006863:Hydrogen-Ion Concentration; D047029:Lactams, Macrocyclic / Q000633:toxicity*; D007893:Leishmania donovani / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development*; D017382:Reactive Oxygen Species / Q000032:analysis
D000975:Antioxidants; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D017382:Reactive Oxygen Species; D005978:Glutathione; C001277:geldanamycin
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