Propofol induces apoptosis by activating caspases and the MAPK pathways, and inhibiting the Akt pathway in TM3 mouse Leydig stem/progenitor cells

Kang,Fu‑Chi; Chen,Yun‑Chia; Wang,Shu‑Chun; So,Edmund   Cheung; Huang,Bu‑Miin

doi:10.3892/ijmm.2020.4584

Propofol induces apoptosis by activating caspases and the MAPK pathways, and inhibiting the Akt pathway in TM3 mouse Leydig stem/progenitor cells

Authors:
- Fu‑Chi Kang
- Yun‑Chia Chen
- Shu‑Chun Wang
- Edmund Cheung So
- Bu‑Miin Huang
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Affiliations: Department of Anesthesia, Chi Mei Medical Center, Chiali, Tainan 71004, Taiwan, R.O.C., Department of Anatomy, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C., Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C., Department of Anesthesia, An Nan Hospital, China Medical University, Tainan 70965, Taiwan, R.O.C.
Published online on: April 21, 2020 https://doi.org/10.3892/ijmm.2020.4584
Pages: 439-448

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Abstract

Propofol is an anesthetic agent moderating GABA receptors in the nervous system. A number of studies have demonstrated that propofol exerts a negative effect on neural stem cell development in the neonatal mouse hippocampus. However, to the best of our knowledge, there is no study available to date illustrating whether neonatal exposure to propofol affects Leydig stem/progenitor cell development for normal male reproductive development and functions, and the regulatory mechanism remains elusive. In the present study, TM3 cells, a mouse Leydig stem/progenitor cell line, was treated with propofol. The data illustrated that propofol significantly reduced TM3 cell viability. TM3 subG1 phase cell numbers were significantly increased by propofol assayed by flow cytometric analysis. Annexin V/PI double staining assay of the TM3 Leydig cells also demonstrated that propofol increased TM3 cell apoptosis. In addition, cleaved caspase‑8, ‑9 and ‑3 and/or poly(ADP‑ribose) polymerase (PARP) were significantly activated by propofol in the TM3 cells. Furthermore, the expression levels of phospho‑JNK, phospho‑ERK1/2 and phospho‑p38 were activated by propofol in the TM3 cells, indicating that propofol induced apoptosis through the mitogen‑activated protein kinase (MAPK) pathway. Additionally, propofol diminished the phosphorylation of Akt to increase the apoptosis of TM3 cells. On the whole, the findings of the present study demonstrate that propofol induces TM3 cell apoptosis by activating caspases and MAPK pathways, as well as by inhibiting the Akt pathway in TM3 cells. These findings illustrate that propofol affects the viability of Leydig stem/progenitor cells possibly related to the development of the male reproductive system.

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