Manganese metabolism in humans

被引:367
作者
Chen, Pan [1 ]
Bornhorst, Julia [2 ]
Aschner, Michael [1 ]
机构
[1] Albert Einstein Coll Med, Dept Mol Pharmacol, Forchheimer 209,1300 Morris Pk Ave, Bronx, NY 10461 USA
[2] Univ Potsdam, Inst Nutr Sci, Dept Food Chem, D-14558 Nuthetal, Germany
来源
FRONTIERS IN BIOSCIENCE-LANDMARK | 2018年 / 23卷
关键词
Manganese; Metal Metabolism; Homeostasis; Blood-Brain Barrier; Neurotoxicity; Transporters; Review; BLOOD-BRAIN-BARRIER; IRON TRANSPORTER FERROPORTIN; DIVALENT METAL TRANSPORTER-1; DOPAMINE TRANSPORTER; ALPHA-SYNUCLEIN; INTRACELLULAR TRAFFICKING; MAGNETIC-RESONANCE; PARKINSONS-DISEASE; INFANT FORMULAS; EFFLUX TRANSPORTER;
D O I
10.2741/4665
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Manganese (Mn) is an essential nutrient for intracellular activities; it functions as a cofactor for a variety of enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase and Mn superoxide dismutase (Mn-SOD). Through these metalloproteins, Mn plays critically important roles in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activities. Mn deficiency is rare. In contrast Mn poisoning may be encountered upon overexposure to this metal. Excessive Mn tends to accumulate in the liver, pancreas, bone, kidney and brain, with the latter being the major target of Mn intoxication. Hepatic cirrhosis, polycythemia, hypermanganesemia, dystonia and Parkinsonism-like symptoms have been reported in patients with Mn poisoning. In recent years, Mn has come to the forefront of environmental concerns due to its neurotoxicity. Molecular mechanisms of Mn toxicity include oxidative stress, mitochondrial dysfunction, protein misfolding, endoplasmic reticulum (ER) stress, autophagy dysregulation, apoptosis, and disruption of other metal homeostasis. The mechanisms of Mn homeostasis are not fully understood. Here, we will address recent progress in Mn absorption, distribution and elimination across different tissues, as well as the intracellular regulation of Mn homeostasis in cells. We will conclude with recommendations for future research areas on Mn metabolism.
引用
收藏
页码:1655 / 1679
页数:25
相关论文
共 173 条
[1]   Overview and introduction: The blood-brain barrier in health and disease [J].
Abbott, N. Joan ;
Friedman, Alon .
EPILEPSIA, 2012, 53 :1-6
[2]  
AISEN P, 1978, J BIOL CHEM, V253, P1930
[3]   Inhibition of DAT function attenuates manganese accumulation in the globus pallidus [J].
Anderson, Joel G. ;
Cooney, Paula T. ;
Erikson, Keith M. .
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, 2007, 23 (02) :179-184
[4]  
[Anonymous], 2012, ATSDR TOX PROF MANG
[5]  
[Anonymous], 2001, E TABLE V TABLE DIET
[6]  
Aschner Judy L., 2005, Molecular Aspects of Medicine, V26, P353, DOI 10.1016/j.mam.2005.07.003
[7]   MANGANESE TRANSPORT ACROSS THE BLOOD-BRAIN-BARRIER - RELATIONSHIP TO IRON HOMEOSTASIS [J].
ASCHNER, M ;
ASCHNER, JL .
BRAIN RESEARCH BULLETIN, 1990, 24 (06) :857-860
[8]   Manganese: Recent advances in understanding its transport and neurotoxicity [J].
Aschner, Michael ;
Guilarte, Tomas R. ;
Schneider, Jay S. ;
Zheng, Wei .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2007, 221 (02) :131-147
[9]   Metal Transporter Zip14 (Slc39a14) Deletion in Mice Increases Manganese Deposition and Produces Neurotoxic Signatures and Diminished Motor Activity [J].
Aydemir, Tolunay Beker ;
Kim, Min-Hyun ;
Kim, Jinhee ;
Colon-Perez, Luis M. ;
Banan, Guita ;
Mareci, Thomas H. ;
Febo, Marcelo ;
Cousins, Robert J. .
JOURNAL OF NEUROSCIENCE, 2017, 37 (25) :5996-6006
[10]   Regional cerebral metabolism in mouse under chronic manganese exposure: Implications for Manganism [J].
Bagga, Puneet ;
Patel, Anant Bahadur .
NEUROCHEMISTRY INTERNATIONAL, 2012, 60 (02) :177-185