PMID- 28578006 OWN - NLM STAT- MEDLINE DCOM- 20180322 LR - 20180322 IS - 1879-3177 (Electronic) IS - 0887-2333 (Linking) VI - 43 DP - 2017 Sep TI - Increased Sat2 expression is associated with busulfan-induced testicular Sertoli cell injury. PG - 47-57 LID - S0887-2333(17)30148-0 [pii] LID - 10.1016/j.tiv.2017.05.023 [doi] AB - Busulfan is a chemotherapeutic agent used to treat chronic myelogenous leukemia and other myeloproliferative disorders. Increasing evidence has demonstrated that busulfan may induce testicular dysfunction by targeting genes that are expressed in the testis. Here, we showed that spermidine/spermine N1-acetyltransferase 2 (Sat2) was present in testicular Sertoli cells, and its expression was significantly increased by busulfan treatment. To investigate the implications of Sat2 upregulation for cell growth and function, a Sat2-overexpressing TM4 Sertoli cell model was established. Increased Sat2 expression led to inhibited cell proliferation and arrested cell cycle. Based on iTRAQ proteomics analysis, we revealed that Sat2 overexpression is detrimental to cell cycle progression and cell communication, and notably, Sat2 may disturb protein metabolic processes by altering translation regulation and protein complex subunit organization. In summary, the present study provides evidence that Sat2 upregulation induces alterations in the growth and function of Sertoli cells. In testis tissue subjected to busulfan, increased expression of Sat2 can cause cellular injury and subsequent organ damage, which could lead to male infertility. Therefore, Sat2 may be a novel molecular target for treating busulfan-induced testicular toxicity. CI - Copyright (c) 2017. Published by Elsevier Ltd. FAU - Xian, Yi AU - Xian Y AD - Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. FAU - Wu, Mingjun AU - Wu M AD - Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. FAU - Liu, Yaping AU - Liu Y AD - Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. FAU - Hao, Jie AU - Hao J AD - The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. FAU - Wu, Yu AU - Wu Y AD - Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. FAU - Liao, Xiaogang AU - Liao X AD - Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. FAU - Li, Gang AU - Li G AD - Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. Electronic address: lg168sn@sina.com. LA - eng PT - Journal Article DEP - 20170601 PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (Antineoplastic Agents, Alkylating) RN - EC 2.3.1.- (Acetyltransferases) RN - EC 2.3.1.57 (diamine N-acetyltransferase) RN - G1LN9045DK (Busulfan) SB - IM MH - Acetyltransferases/genetics/*metabolism MH - Animals MH - Antineoplastic Agents, Alkylating/*toxicity MH - Busulfan/*toxicity MH - Cell Line MH - Cell Survival/drug effects MH - Male MH - Mice, Inbred C57BL MH - Testis/*drug effects/metabolism/pathology OTO - NOTNLM OT - Busulfan OT - Sat2 OT - Sertoli cells EDAT- 2017/06/05 06:00 MHDA- 2018/03/23 06:00 CRDT- 2017/06/05 06:00 PHST- 2017/01/03 00:00 [received] PHST- 2017/05/16 00:00 [revised] PHST- 2017/05/31 00:00 [accepted] PHST- 2017/06/05 06:00 [pubmed] PHST- 2018/03/23 06:00 [medline] PHST- 2017/06/05 06:00 [entrez] AID - S0887-2333(17)30148-0 [pii] AID - 10.1016/j.tiv.2017.05.023 [doi] PST - ppublish SO - Toxicol In Vitro. 2017 Sep;43:47-57. doi: 10.1016/j.tiv.2017.05.023. Epub 2017 Jun 1.