title: Midazolam induces apoptosis in MA-10 mouse Leydig tumor cells through caspase activation and the involvement of MAPK signaling pathway.
abstract: OBJECTIVE
  The present study aims to investigate how midazolam, a sedative drug for clinical use with cytotoxicity on neuronal and peripheral tissues, induced apoptosis in MA-10 mouse Leydig tumor cells.
  
  
  METHODS
  The apoptotic effect and underlying mechanism of midazolam to MA-10 cells were investigated by flow cytometry assay and Western blotting methods.
  
  
  RESULTS
  Data showed that midazolam induced the accumulation of the MA-10 cell population in the sub-G1 phase and a reduction in the G2/M phase in a time- and dose-dependent manner, suggesting an apoptotic phenomenon. Midazolam could also induce the activation of caspase-8, -9, and -3 and poly (ADP-ribose) polymerase proteins. There were no changes in the levels of Bax and cytochrome-c, whereas Bid was significantly decreased after midazolam treatment. Moreover, midazolam decreased both pAkt and Akt expression. In addition, midazolam stimulated the phosphorylation of p38 and c-Jun NH2-terminal kinase but not extracellular signal-regulated kinase.
  
  
  CONCLUSIONS
  Midazolam could induce MA-10 cell apoptosis through the activation of caspase cascade, the inhibition of pAkt pathway, and the induction of p38 and c-Jun NH2-terminal kinase pathways.
authors.affiliation: Department of Anesthesia, Tainan Municipal An Nan Hospital, China Medical University, Tainan, Taiwan ; Department of Anesthesia, China Medical University, Taichung, Taiwan.
authors.forename: Edmund Cheung
authors.initials: EC
authors.lastname: So
authors.affiliation: Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Xuan
authors.initials: YX
authors.lastname: Lin
authors.affiliation: Department of Anesthesia, Tainan Municipal An Nan Hospital, China Medical University, Tainan, Taiwan.
authors.forename: Chi Hao
authors.initials: CH
authors.lastname: Tseng
authors.affiliation: Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Bo-Syong
authors.initials: BS
authors.lastname: Pan
authors.affiliation: Department of Anesthesia, China Medical University, Taichung, Taiwan.
authors.forename: Ka-Shun
authors.initials: KS
authors.lastname: Cheng
authors.affiliation: Department of Anesthesia, China Medical University, Taichung, Taiwan.
authors.forename: Kar-Lok
authors.initials: KL
authors.lastname: Wong
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Kaohsiung Veteran General Hospital Tainan Branch Tainan, Taiwan.
authors.forename: Lyh-Jyh
authors.initials: LJ
authors.lastname: Hao
authors.affiliation: Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yang-Kao
authors.initials: YK
authors.lastname: Wang
authors.affiliation: Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Bu-Miin
authors.initials: BM
authors.lastname: Huang
keywords: Akt; MA-10 cell; MAPKs; apoptosis; caspase; midazolam