PMID- 30260385 OWN - NLM STAT- MEDLINE DCOM- 20190311 LR - 20211204 IS - 1745-7270 (Electronic) IS - 1672-9145 (Linking) VI - 50 IP - 11 DP - 2018 Nov 1 TI - Organosulfur compounds induce cytoprotective autophagy against apoptosis by inhibiting mTOR phosphorylation activity in macrophages. PG - 1085-1093 LID - 10.1093/abbs/gmy114 [doi] AB - Organosulfur compounds (OSCs) are the bioactive components of garlic. Some OSCs have apoptotic or autophagy-inducing effects. Autophagy plays roles in both cytoprotection and apoptosis-related cell death, and the interaction between autophagy and apoptosis is important in the modulation of immune responses. The mechanism of an OSC-mediated effect via the interaction of autophagy and apoptosis is unknown. In this study, the effects of five OSC compounds on autophagy in the macrophage cell line RAW264.7 and primary macrophages were investigated. We found that S-allylcysteine (SAC), diallyl disulde (DADS) and diallyl tetrasulfide (DTS) treatment increased the number of autophagosomes of RAW264.7 cells, inhibited the phosphorylation of ribosomal protein S6 kinase beta-1 (p70S6K/S6K1) which is a substrate of mammalian target of rapamycin (mTOR), and significantly enhanced autophagy flux. The induction of autophagy by SAC, DADS and DTS was inhibited by stably knocking down the expression of autophagy-related gene 5 (ATG5) with short hairpin RNA (shRNA). Further experiments confirmed that SAC, DADS and DTS also induced apoptosis in RAW264.7 cells. The induction of apoptosis and Caspase 3 activity by SAC, DADS and DTS were increased by stably knocking down of ATG5 expression with shRNA in RAW264.7 cells or treating with 5 mM 3-MA in primary macrophages. Our results suggest that SAC, DADS and DTS induce both autophagy and apoptosis. The autophagy induction protects macrophages from apoptosis by inhibiting mTOR phosphorylation activity to maintain the mass of immune cells. FAU - Wu, Yanyang AU - Wu Y AD - College of Food Science and Technology, Hunan Agricultural University, Changsha, China. FAU - Hu, Yongquan AU - Hu Y AD - Horticulture and Landscape College, Hunan Agricultural University, Changsha, China. AD - Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients, Changsha, China. AD - State Key Laboratory of Subhealth Intervention Technology, Changsha, China. FAU - Zhou, Haiyan AU - Zhou H AD - Horticulture and Landscape College, Hunan Agricultural University, Changsha, China. AD - Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients, Changsha, China. AD - State Key Laboratory of Subhealth Intervention Technology, Changsha, China. FAU - Zhu, Jiayu AU - Zhu J AD - Horticulture and Landscape College, Hunan Agricultural University, Changsha, China. AD - Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients, Changsha, China. AD - State Key Laboratory of Subhealth Intervention Technology, Changsha, China. FAU - Tong, Zhongyi AU - Tong Z AD - Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, China. FAU - Qin, Si AU - Qin S AD - College of Food Science and Technology, Hunan Agricultural University, Changsha, China. FAU - Liu, Dongbo AU - Liu D AD - Horticulture and Landscape College, Hunan Agricultural University, Changsha, China. AD - Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients, Changsha, China. AD - State Key Laboratory of Subhealth Intervention Technology, Changsha, China. LA - eng PT - Journal Article PL - China TA - Acta Biochim Biophys Sin (Shanghai) JT - Acta biochimica et biophysica Sinica JID - 101206716 RN - 0 (Allyl Compounds) RN - 0 (Disulfides) RN - 0 (Organic Chemicals) RN - 0 (Protective Agents) RN - 0 (Sulfides) RN - 0 (Sulfur Compounds) RN - 5HI47O6OA7 (diallyl disulfide) RN - 81R3X99M15 (S-allylcysteine) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - K848JZ4886 (Cysteine) RN - WRP12IW1D7 (diallyl tetrasulfide) SB - IM MH - Allyl Compounds/pharmacology MH - Animals MH - Apoptosis/*drug effects MH - Autophagosomes/drug effects/metabolism MH - Autophagy/*drug effects MH - Cells, Cultured MH - Cysteine/analogs & derivatives/pharmacology MH - Disulfides/pharmacology MH - Garlic/chemistry MH - Macrophages/cytology/*drug effects/metabolism MH - Mice MH - Organic Chemicals/*pharmacology MH - Phosphorylation/drug effects MH - Protective Agents/pharmacology MH - RAW 264.7 Cells MH - Sulfides/pharmacology MH - Sulfur Compounds/*pharmacology MH - TOR Serine-Threonine Kinases/*metabolism EDAT- 2018/09/28 06:00 MHDA- 2019/03/12 06:00 CRDT- 2018/09/28 06:00 PHST- 2018/03/13 00:00 [received] PHST- 2018/09/28 06:00 [pubmed] PHST- 2019/03/12 06:00 [medline] PHST- 2018/09/28 06:00 [entrez] AID - 5107347 [pii] AID - 10.1093/abbs/gmy114 [doi] PST - ppublish SO - Acta Biochim Biophys Sin (Shanghai). 2018 Nov 1;50(11):1085-1093. doi: 10.1093/abbs/gmy114.