Article
Hematology
Vida Zhang, Supak Jenkitkasemwong, Qingli Liu, Tomas Ganz, Elizabeta Nemeth, Mitchell D. Knutson, Airie Kim
Summary: ZIP8 is a transmembrane protein that imports divalent metal ions and is highly expressed in the lung. It can transport iron and is inducible by inflammatory stimuli. This study found that ZIP8 plays a role in systemic iron homeostasis and transports iron from the airway into lung tissue, but it does not modulate the severity of inflammatory lung injury or the host defense against a common bacterial cause of pneumonia.
Article
Biochemistry & Molecular Biology
Robert G. Mealer, Sarah E. Williams, Maxence Noel, Bo Yang, Alexandria K. D'Souza, Toru Nakata, Daniel B. Graham, Elizabeth A. Creasey, Murat Cetinbas, Ruslan I. Sadreyev, Edward M. Scolnick, Christina M. Woo, Jordan W. Smoller, Ramnik J. Xavier, Richard D. Cummings
Summary: The missense mutation A391T in SLC39A8 is strongly associated with schizophrenia, and this study reveals its impact on protein glycosylation in the brain. This finding provides a mechanistic link between the risk allele and reversible biochemical changes, offering a new understanding of the molecular pathophysiology of schizophrenia and a potential avenue for therapeutic development.
MOLECULAR PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Suetmui Yu, Ningning Zhao
Summary: ZIP8 is a newly discovered manganese transporter that plays a crucial role in maintaining body manganese homeostasis. This study investigated the regulation of ZIP8 by high-manganese intake using mouse models. The results revealed that high dietary manganese intake leads to a decrease in ZIP8 protein in the liver of young mice, which prevents manganese overload. Additionally, the study found an age-dependent variation in the expression of ZIP8 in the liver of adult animals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Clinical Neurology
Dipti Kapoor, Divyani Garg, Suvasini Sharma, Vinay Goyal
Summary: Although acquired manganese neurotoxicity has been widely reported for many years, inherited disorders of manganese homeostasis were only discovered in 2012, mainly affecting children and adolescents. Mutations in manganese transporter genes can lead to either manganese overload or deficiency, causing neurological issues that require different treatment approaches.
ANNALS OF INDIAN ACADEMY OF NEUROLOGY
(2021)
Article
Physiology
Sophia N. Verouti, Jonai Pujol-Gimenez, Paola Bermudez-Lekerika, Laeticia Scherler, Rajesh Bhardwaj, Aurelien Thomas, Sebastien Lenglet, Mark Siegrist, Willy Hofstetter, Daniel G. Fuster, Matthias A. Hediger, Genevieve Escher, Bruno Vogt
Summary: The metal ion transporter ZIP8 has been found to play a significant role in blood pressure regulation and glucose homeostasis. The SNP variant A391T (rs13107325) of ZIP8 is associated with reduced arterial blood pressure and insulin resistance, but not with body weight and plasma lipid composition. This research also suggests that ZIP8 is involved in the cellular uptake of zinc, cadmium, and iron.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cell Biology
Karin Tuschl, Richard J. White, Chintan Trivedi, Leonardo E. Valdivia, Stephanie Niklaus, Isaac H. Bianco, Chris Dadswell, Ramon Gonzalez-Mendez, Ian M. Sealy, Stephan C. F. Neuhauss, Corinne Houart, Jason Rihel, Stephen W. Wilson, Elisabeth M. Busch-Nentwich
Summary: This study identified potential targets of manganese neurotoxicity using a slc39a14(-/-) mutant zebrafish model exposed to MnCl2. The findings suggest that dysregulation of Ca2+ homeostasis and activation of the unfolded protein response are key features of manganese neurotoxicity. Additionally, manganese exposure led to locomotor defects and changes in visual and neuronal activity.
DISEASE MODELS & MECHANISMS
(2022)
Review
Biochemistry & Molecular Biology
Alexander N. Rodichkin, Tomas R. Guilarte
Summary: Clinical reports on childhood-onset manganese-induced dystonia-parkinsonism have provided valuable insights, but our understanding of the underlying neuropathophysiology remains limited. The availability of Slc39a14 knockout animal models offers a powerful platform for further research into the neurological effects of elevated manganese concentrations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Jonai Pujol-Gimenez, Marion Poirier, Sven Buehlmann, Celine Schuppisser, Rajesh Bhardwaj, Mahendra Awale, Ricardo Visini, Sacha Javor, Matthias A. Hediger, Jean-Louis Reymond
Summary: Researchers discovered the first inhibitor of ZIP8, showing that this target is druggable, through screening a library of molecules in a database.
Article
Neurosciences
Alexander N. Rodichkin, Melissa K. Edler, Jennifer L. McGlothan, Tomas R. Guilarte
Summary: Studies in Slc39a14-KO mice as a preclinical model of dystonia-Parkinsonism in SLC39A14 mutation carriers show elevated blood and brain metal concentrations similar to the human disease, with impaired locomotor activity and motor coordination. The dysfunction in dopamine release in the striatum suggests involvement of other neuronal systems and brain regions in the pathophysiology of the disease.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Cell Biology
Derrick R. Samuelson, Sabah Haq, Daren L. Knoell
Summary: Manganese and zinc are essential micronutrients that play a crucial role in regulating host immune response against infections. The metal transporter ZIP8 plays a key role in metal uptake and affects host defense mechanisms. Perturbations in metal homeostasis may impact the composition of bacterial communities in the host. Therefore, understanding the importance of zinc and manganese uptake is important for the development of intervention strategies against infectious diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hitomi Fujishiro, Sara Miyamoto, Daigo Sumi, Taiho Kambe, Seiichiro Himeno
Summary: The study revealed the associations between ZIP8 transporter and various human diseases, and the different effects of four mutations on the transporting activity of manganese and cadmium. By utilizing DT40 cells, the roles of individual residues in metal transport were clarified more clearly.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Immunology
Guojun Wei, Yuze Wu, Ningning Zhao
Summary: ZIP8 is a newly identified metal transporter critical in regulating systemic manganese homeostasis, with mutations causing severe deficiency. Studies using mice were limited by the lack of suitable antibodies until the successful generation and validation of an anti-mouse ZIP8 antibody, providing opportunities for further research. This development may also offer insights into future antibody development targeting polytopic membrane proteins.
Article
Toxicology
Stephanie Probst, Johannes Fels, Bettina Scharner, Natascha A. Wolff, Eleni Roussa, Rachel P. L. van Swelm, Wing-Kee Lee, Frank Thevenod
Summary: Hepcidin plays a critical role in protecting against Fe2+-induced cell death in the kidney, while exacerbating oxidative stress and cell death caused by Cd2+. The differential effects of hepcidin on Fe2+ and Cd2+ toxicity are mediated by its impact on catalase activity, ROS levels, and downstream cell processes.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Neurosciences
Genesys Giraldo, Christopher Janus
Summary: Research characterized a mouse model of childhood-onset parkinsonism-dystonia caused by a mutation in the SLC39A14 gene, showing a complex pathological motor phenotype with impaired locomotor behavior and postural abnormalities. Despite displaying postural abnormalities like torticollis and Straub tail, the mice's performance in motor tests remained unaffected.
BRAIN RESEARCH BULLETIN
(2021)
Article
Biology
Yuhan Jiang, Zhen Li, Dexin Sui, Gaurav Sharma, Tianqi Wang, Keith MacRenaris, Hideki Takahashi, Kenneth Merz, Jian Hu
Summary: An integrated experimental and computational approach was used to study the substrate selectivity of the multi-metal transporter ZIP8. By rationally engineering the transporter, a zinc-preferring variant was created, which showed reduced transport activities towards other metals and increased activity towards zinc. The study revealed a conditional selectivity filter in the transporter and provided knowledge about substrate specificity, which can be applied to other transporter engineering and mechanistic studies.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Manigandan Nagarajan, Gobichettipalayam Balasubramaniam Maadurshni, Jeganathan Manivannan
Summary: This study found that exposure to BPA exacerbates hypertension-induced pathological changes, including renal fibrosis, oxidative stress, elevated angiotensin-converting enzyme activity, dysfunction of antioxidant and tricarboxylic acid cycle enzymes, tissue lipid abnormalities, and expression of inflammatory factors. In addition, high levels of BPA have dose-dependent effects on kidney cells, including oxidative stress, mitochondrial dysfunction, and lipid peroxidation. Therefore, a precise investigation of BPA exposure in hypertensive populations is highly recommended during risk assessment.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2024)
Article
Biochemistry & Molecular Biology
Haiping Bao, Qiang Zhang, Yu Li, Chen Nie
Summary: In this study, the role of circDLGAP4 in Parkinson's disease (PD) was investigated. The results showed that circDLGAP4 upregulated HMGA2 by recruiting EIF4A3, thus alleviating neuronal injury in PD.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2024)
Article
Biochemistry & Molecular Biology
Lina Yang, Tianwei He, Yanming Yu
Summary: This study found that uric acid induces kidney injury by inducing IL-17 expression, and treatment with anti-IL-17 antibody can alleviate uric acid-induced kidney injury.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2024)
Article
Biochemistry & Molecular Biology
Ediandra T. Castro, Amalia G. Alves, Daniela de Bittencourt Maia, Larissa S. Magalhaes, Mariana P. Paim, Filipe Penteado, Caroline S. Gomes, Eder J. Lenardao, Cesar A. Bruning, Cristiani F. Bortolatto
Summary: This study investigated the antioxidant activity and toxicity of selenium-containing compounds in liver tissue. The results showed that these compounds have potential antioxidant effects, which can be attributed to their ability to scavenge free radicals and mimic enzyme activity. Additionally, one of the compounds exhibited low toxicity.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2024)