PMID- 30704032 OWN - NLM STAT- MEDLINE DCOM- 20190513 LR - 20200225 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 3 DP - 2019 Jan 30 TI - Lactoferrin Induces the Synthesis of Vitamin B6 and Protects HUVEC Functions by Activating PDXP and the PI3K/AKT/ERK1/2 Pathway. LID - 10.3390/ijms20030587 [doi] LID - 587 AB - As a nutritional active protein in foods, multiple studies of the biological activities of lactoferrin had been undertaken, including antioxidant, antiviral, anti-inflammatory, antitumor, antibiosis, and antiparasitic effects, while the mechanism related with its protection of cardiovascular system remained elusive. In the present work, the effect of lactoferrin on the viability of HUVECs (human umbilical vein endothelial cells) was detected to select the proper doses. Moreover, transcriptomics detection and data analysis were performed to screen out the special genes and the related pathways. Meanwhile, the regulation of lactoferrin in the functional factors thromboxane A(2) (TXA(2)) and prostacyclin (PGI(2)) was detected. Then, the small interfering RNA (SiRNA) fragment of the selected gene pyridoxal phosphatase (PDXP) was transfected into HUVECs to validate its role in protecting HUVECs function. Results showed that lactoferrin inhibited the expression of TXA2 and activated expression of PGI(2), as well as activated expression of PDXP, which significantly up-regulated the synthesis of vitamin B6 (VB6) and the phosphoinositide 3-kinase (PI3K)/ serine/threonine-protein kinase (AKT)/ extracellular regulated protein kinases (ERK) 1/2 pathway. For the first time, we revealed that lactoferrin could induce the synthesis of VB6 and protect HUVECs function through activating PDXP gene and the related pathway. FAU - Li, Huiying AU - Li H AD - State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. thufit2012@126.com. AD - Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. thufit2012@126.com. AD - Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. thufit2012@126.com. FAU - Wang, Yizhen AU - Wang Y AD - State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. m13613613572_2@163.com. AD - Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. m13613613572_2@163.com. AD - Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. m13613613572_2@163.com. FAU - Yang, Huaigu AU - Yang H AD - State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. yanghgxms@163.com. AD - Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. yanghgxms@163.com. AD - Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. yanghgxms@163.com. FAU - Liu, Li AU - Liu L AD - State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. liliu0324@126.com. AD - Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. liliu0324@126.com. AD - Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. liliu0324@126.com. FAU - Wang, Jiaqi AU - Wang J AD - State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. wangjiaqi@caas.cn. AD - Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. wangjiaqi@caas.cn. AD - Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. wangjiaqi@caas.cn. FAU - Zheng, Nan AU - Zheng N AD - State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. zhengnan_1980@126.com. AD - Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. zhengnan_1980@126.com. AD - Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. zhengnan_1980@126.com. LA - eng GR - 201403071/Special Fund for Agro-scientific Research in the public Interest/ GR - CARS-36/the Ministry of Modern Agro-Industry Technology Research System of China/ GR - ASTIP-IAS12/the Agricultural Science and Technology Innovation Program/ PT - Journal Article DEP - 20190130 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 57576-52-0 (Thromboxane A2) RN - 8059-24-3 (Vitamin B 6) RN - DCR9Z582X0 (Epoprostenol) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 3.1.3.16 (PDXP protein, human) RN - EC 3.1.3.16 (Phosphoprotein Phosphatases) RN - EC 3.4.21.- (Lactoferrin) SB - IM MH - Cell Survival/*drug effects MH - Enzyme-Linked Immunosorbent Assay MH - Epoprostenol/metabolism MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Lactoferrin/*pharmacology MH - MAP Kinase Signaling System/*drug effects MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Phosphoprotein Phosphatases/*metabolism MH - Thromboxane A2/metabolism MH - Vitamin B 6/*metabolism PMC - PMC6387185 OTO - NOTNLM OT - HUVEC OT - PDXP OT - PGI2 OT - TXA2 OT - lactoferrin OT - vitamin B6 COIS- The authors declare no conflict of interest. EDAT- 2019/02/02 06:00 MHDA- 2019/05/14 06:00 PMCR- 2019/02/01 CRDT- 2019/02/02 06:00 PHST- 2018/12/22 00:00 [received] PHST- 2019/01/18 00:00 [revised] PHST- 2019/01/26 00:00 [accepted] PHST- 2019/02/02 06:00 [entrez] PHST- 2019/02/02 06:00 [pubmed] PHST- 2019/05/14 06:00 [medline] PHST- 2019/02/01 00:00 [pmc-release] AID - ijms20030587 [pii] AID - ijms-20-00587 [pii] AID - 10.3390/ijms20030587 [doi] PST - epublish SO - Int J Mol Sci. 2019 Jan 30;20(3):587. doi: 10.3390/ijms20030587.