title: The protective effect of lactoferrin on ventral mesencephalon neurons against MPP + is not connected with its iron binding ability.
abstract: Lactoferrin (Lf) can bind to lactoferrin receptor (LfR), leading to iron transport through the plasma membrane. Besides iron transportation, Lf also has antioxidant and anti-inflammatory properties. In the brain, Lf is only synthesized by activated microglia. LfR is present in blood vessels and nigral dopaminergic neurons. Both nigral iron accumulation and microglia activation is believed to be involved in Parkinson's disease (PD), moreover, increased Lf and LfR in dopaminergic neurons were found in PD cases and MPTP-intoxicated mice. How iron influences microglia to release Lf? Does Lf tend to transport iron to dopaminergic neurons leading to cell death or to protect dopaminergic neuron from neurotoxin? In this study, we observed that iron increased Lf synthesis in activated microglia. In ventral mesencephalon neurons, both iron-free Lf (apo-Lf) and iron-saturated Lf (holo-Lf) exerted neuroprotective effects against MPP(+) by mechanisms, believed to enhance the mitochondrial transmembrane potential, improve Cu/Zn-superoxide dismutase activity, increase Bcl-2 expression. Although apo-Lf but not holo-Lf chelated cellular iron, there was no difference between the two types of Lf in the neuroprotection. Our data indicate that iron overload increases the activated microglia releasing Lf. Lf plays protective role on ventral mesencephalon neurons against MPP(+), which is iron-chelating independent.
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao 266071, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao 266071, China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Bi
authors.affiliation: Class 11, Grade 2012, Medical College of Qingdao University, Qingdao 266071, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao 266071, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Song
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao 266071, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Xie
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D007501:Iron / Q000378:metabolism*; D007781:Lactoferrin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008636:Mesencephalon / Q000166:cytology* / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051028:bcl-2-Associated X Protein; C038340:lactoferrin receptors; D007501:Iron; D013482:Superoxide Dismutase; D007781:Lactoferrin