Lactoferrin Induces the Synthesis of Vitamin B6 and Protects HUVEC Functions by Activating PDXP and the PI3K/AKT/ERK1/2 Pathway

Abstract

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 A2 (TXA2) and prostacyclin (PGI2) 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 PGI2, 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.

Maternal serum-derived exosomal lactoferrin as a marker in detecting and predicting ventricular septal defect in fetuses

“…18 More specifically, LTF could trigger the biosynthesis of vitamin B6 and protect cardiovascular function via activating the ERK1/2 and PI3K/AKT cascade. 19 LTF, a glycoprotein, participates in numerous biological processes, such as antioxidant, antiinflammatory, and anti-cancer activities. 20 Results obtained by other investigations have documented a negative impact of inflammation factors on fetal development.…”

Enteral Lactoferrin Administration Attenuates Myocardial Ischemia-Reperfusion Injury in an Isolated Rat Heart Model

“…Enteral administration of lactoferrin attenuated intestinal and cerebral IR injury in rats in previous studies [17,18]. However, while lactoferrin activates the PI3K/Akt signaling pathway [19,20], the relationship between the cardioprotective effects of lactoferrin and the PI3K/Akt signaling pathway in isolated stunned rat hearts remains unknown.…”

Lactoferrin and Its Potential Impact for the Relief of Pain: A Preclinical Approach

“…endothelial cells [96]. Moreover, Lf induced the activation of AKT in human breast adenocarcinoma (MCF) cells; however, the treatment of MCF cells with a PI3K inhibitor almost completely blocked Lf-stimulated cell cycle progression [97].…”

“…There has been no evidence that Lf can activate the PI3K–AKT signaling pathway in animal models of pain. In vitro studies have suggested that Lf downregulates thromboxane 2 (TXA2) and upregulates prostacyclin 2 (PGI2) through activating the PI3K–AKT–ERK1/2 signaling pathway in human umbilical vein endothelial cells [ 96 ]. Moreover, Lf induced the activation of AKT in human breast adenocarcinoma (MCF) cells; however, the treatment of MCF cells with a PI3K inhibitor almost completely blocked Lf-stimulated cell cycle progression [ 97 ].…”