PMID- 27231847 OWN - NLM STAT- MEDLINE DCOM- 20180227 LR - 20181202 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 25 DP - 2016 Jun 21 TI - EAAT3 promotes amino acid transport and proliferation of porcine intestinal epithelial cells. PG - 38681-38692 LID - 10.18632/oncotarget.9583 [doi] AB - Excitatory amino acid transporter 3 (EAAT3, encoded by SLC1A1) is an epithelial type high-affinity anionic amino acid transporter, and glutamate is the major oxidative fuel for intestinal epithelial cells. This study investigated the effects of EAAT3 on amino acid transport and cell proliferation through activation of the mammalian target of the rapamycin (mTOR) pathway in porcine jejunal epithelial cells (IPEC-J2). Anionic amino acid and cystine (Cys) transport were increased (P<0.05) by EAAT3 overexpression and decreased (P<0.05) by EAAT3 knockdown rather than other amino acids. MTT and cell counting assays suggested that IPEC-J2 cell proliferation increased (P<0.05) with EAAT3 overexpression. Phosphorylation of mTOR (Ser2448), ribosomal protein S6 kinase-1 (S6K1, Thr389) and eukaryotic initiation factor 4E-binding protein-1 (4EBP1, Thr70) was increased by EAAT3 overexpression and decreased by EAAT3 knockdown (P<0.05), as were levels of activating transcription factor 4 (ATF4) and cystine/glutamate antiporter (xCT) (P<0.05). Our results demonstrate for the first time that EAAT3 facilitates anionic amino acid transport and activates the mTOR pathway, promoting Cys transport and IPEC-J2 cell proliferation. FAU - Ye, Jin-Ling AU - Ye JL AD - College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou, Guangdong Province, China. FAU - Gao, Chun-Qi AU - Gao CQ AD - College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou, Guangdong Province, China. FAU - Li, Xiang-Guang AU - Li XG AD - College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou, Guangdong Province, China. FAU - Jin, Cheng-Long AU - Jin CL AD - College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou, Guangdong Province, China. FAU - Wang, Dan AU - Wang D AD - College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou, Guangdong Province, China. FAU - Shu, Gang AU - Shu G AD - College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou, Guangdong Province, China. FAU - Wang, Wen-Ce AU - Wang WC AD - College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou, Guangdong Province, China. FAU - Kong, Xiang-Feng AU - Kong XF AD - Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan Province, China. FAU - Yao, Kang AU - Yao K AD - Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan Province, China. FAU - Yan, Hui-Chao AU - Yan HC AD - College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou, Guangdong Province, China. FAU - Wang, Xiu-Qi AU - Wang XQ AD - College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou, Guangdong Province, China. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Excitatory Amino Acid Transporter 3) SB - IM MH - Animals MH - Cell Proliferation/physiology MH - Cells, Cultured MH - Epithelial Cells/*metabolism MH - Excitatory Amino Acid Transporter 3/biosynthesis/*metabolism MH - Female MH - Humans MH - Intestinal Mucosa/*metabolism MH - Intestines/cytology MH - Male MH - Swine PMC - PMC5122420 OTO - NOTNLM OT - amino acid OT - excitatory amino acid transporter 3 OT - intestinal epithelial cells OT - mammalian target of rapamycin OT - proliferation COIS- The authors declare no conflicts of interest. EDAT- 2016/10/23 06:00 MHDA- 2018/02/28 06:00 PMCR- 2016/06/21 CRDT- 2016/05/28 06:00 PHST- 2016/02/12 00:00 [received] PHST- 2016/04/29 00:00 [accepted] PHST- 2016/10/23 06:00 [pubmed] PHST- 2018/02/28 06:00 [medline] PHST- 2016/05/28 06:00 [entrez] PHST- 2016/06/21 00:00 [pmc-release] AID - 9583 [pii] AID - 10.18632/oncotarget.9583 [doi] PST - ppublish SO - Oncotarget. 2016 Jun 21;7(25):38681-38692. doi: 10.18632/oncotarget.9583.