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https://www.readbyqxmd.com/read/27782264/metal-homeostasis-disruption-and-mitochondrial-dysfunction-in-hepatocytes-exposed-to-sub-toxic-doses-of-zinc-oxide-nanoparticles
#1
M Chevallet, B Gallet, A Fuchs, P H Jouneau, K Um, E Mintz, I Michaud-Soret
Increased production and use of zinc oxide nanoparticles (ZnO-NPs) in consumer products has prompted the scientific community to investigate their potential toxicity, and understand their impact on the environment and organisms. Molecular mechanisms involved in ZnO-NP toxicity are still under debate and focus essentially on high dose expositions. In our study, we chose to evaluate the effect of sub-toxic doses of ZnO-NPs on human hepatocytes (HepG2) with a focus on metal homeostasis and redox balance disruptions...
October 26, 2016: Nanoscale
https://www.readbyqxmd.com/read/27732669/effects-of-long-term-exposure-to-zinc-oxide-nanoparticles-on-development-zinc-metabolism-and-biodistribution-of-minerals-zn-fe-cu-mn-in-mice
#2
Chao Wang, Jianjun Lu, Le Zhou, Jun Li, Jiaman Xu, Weijian Li, Lili Zhang, Xiang Zhong, Tian Wang
Zinc oxide nanoparticles (nano-ZnOs) are widely used and possess great potentials in agriculture and biomedicine. It is inevitable for human exposure to these nanoparticles. However, no study had been conducted to investigate the long term effects of nano-ZnOs. This study aimed at investigating effects of nano-ZnOs on development, zinc metabolism and biodistribution of minerals (Zn, Fe, Cu, and Mn) in mice from week 3 to 35. After the characteristics of nano-ZnOs were determined, they were added into the basal diet at 0, 50, 500 and 5000 mg/kg...
2016: PloS One
https://www.readbyqxmd.com/read/27422508/metallothionein-and-zinc-transporter-expression-in-circulating-human-blood-cells-as-biomarkers-of-zinc-status-a-systematic-review
#3
REVIEW
Stephen R Hennigar, Alyssa M Kelley, James P McClung
Zinc is an essential nutrient for humans; however, a sensitive biomarker to assess zinc status has not been identified. The objective of this systematic review was to compile and assess studies that determined zinc transporter and/or metallothionein expression in various blood cell types and to determine their reliability and sensitivity to changes in dietary zinc. Sixteen studies were identified that determined the expression of zrt-, irt-like protein (ZIP) 1 [solute carrier family (SLC) 39A1], ZIP3 (SLC39A3), ZIP5 (SLC39A5), ZIP6 (SLC39A6), ZIP7 (SLC39A7), ZIP8 (SLC39A8), ZIP10 (SLC39A10), ZIP14 (SLC39A14), zinc transporter (ZnT)1 (SLC30A1), ZnT2 (SLC30A2), ZnT4 (SLC30A4), ZnT5 (SLC30A5), ZnT6 (SLC30A6), ZnT7 (SLC30A7), ZnT9 (SLC30A9), and/or metallothionein in various blood cells isolated from healthy adult men and women in response to zinc supplementation or depletion...
July 2016: Advances in Nutrition
https://www.readbyqxmd.com/read/27319394/maternal-cadmium-exposure-reduces-placental-zinc-transport-and-induces-fetal-growth-restriction-in-mice
#4
Hua Wang, Ying Wang, Qing-Li Bo, Yan-Li Ji, Lu Liu, Yong-Fang Hu, Yuan-Hua Chen, Jun Zhang, Ling-Li Zhao, De-Xiang Xu
Cadmium (Cd) is linked with increased risk of fetal growth restriction (FGR). Nevertheless, the mechanism remains unknown. This study established a mouse model of Cd-induced FGR through two exposure methods. Pregnant mice were either administered with CdCl2 (5, 50 and 250ppm) throughout pregnancy through drinking water or intraperitoneally injected with CdCl2 (4.5mg/kg) on GD9. As expected, fetal weight and crown-rump length were reduced in a gender-independent manner. Interestingly, Mt1 and Mt2, two metallothionein genes, were up-regulated in maternal liver...
August 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27304099/novel-mutations-in-slc30a2-involved-in-the-pathogenesis-of-transient-neonatal-zinc-deficiency
#5
Naoya Itsumura, Yoshie Kibihara, Kazuhisa Fukue, Akiko Miyata, Kenji Fukushima, Risa Tamagawa-Mineoka, Norito Katoh, Yukina Nishito, Riko Ishida, Hiroshi Narita, Hiroko Kodama, Taiho Kambe
BACKGROUND: Infants are vulnerable to zinc deficiency. Thus, abnormally low breast milk zinc levels cause transient neonatal zinc deficiency (TNZD) in breast-fed infants. TNZD has been considered to be rare because of a paucity of citations in the published literature. However, recent studies of affected mothers identified four missense mutations in the solute carrier family 30 member 2 gene (SLC30A2), which encodes the zinc transporter, ZnT2. METHODS: Genetic analyses of SLC30A2/ZnT2 in three Japanese mothers secreting low-zinc milk (whose infants developed TNZD) were performed...
October 2016: Pediatric Research
https://www.readbyqxmd.com/read/27137936/molecular-basis-of-transient-neonatal-zinc-deficiency-novel-znt2-mutations-disrupting-zinc-binding-and-permeation
#6
Yarden Golan, Naoya Itsumura, Fabian Glaser, Bluma Berman, Taiho Kambe, Yehuda G Assaraf
A gradually increasing number of transient neonatal zinc deficiency (TNZD) cases was recently reported, all of which were associated with inactivating ZnT2 mutations. Here we characterized the impact of three novel heterozygous ZnT2 mutations G280R, T312M, and E355Q, which cause TNZD in exclusively breastfed infants of Japanese mothers. We used the bimolecular fluorescence complementation (BiFC) assay to provide direct visual evidence for the in situ dimerization of these ZnT2 mutants, and to explore their subcellular localization...
June 24, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26598882/overview-of-inherited-zinc-deficiency-in-infants-and-children
#7
REVIEW
Taiho Kambe, Kazuhisa Fukue, Riko Ishida, Shiho Miyazaki
Zinc nutrition is of special practical importance in infants and children. Poor zinc absorption causes zinc deficiency, which leads to a broad range of consequences such as alopecia, diarrhea, skin lesions, taste disorders, loss of appetite, impaired immune function and neuropsychiatric changes and growth retardation, thus potentially threatening life in infants and children. In addition to dietary zinc deficiency, inherited zinc deficiency, which rarely occurs, is found during the infant stage and early childhood...
2015: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/26538236/znt4-slc30a4-null-lethal-milk-mice-have-defects-in-mammary-gland-secretion-and-hallmarks-of-precocious-involution-during-lactation
#8
Nicholas H McCormick, Sooyeon Lee, Stephen R Hennigar, Shannon L Kelleher
During lactation, highly specialized secretory mammary epithelial cells (MECs) produce and secrete huge quantities of nutrients and nonnutritive factors into breast milk. The zinc (Zn) transporter ZnT4 (SLC30A4) transports Zn into the trans-Golgi apparatus for lactose synthesis, and across the apical cell membrane for efflux from MECs into milk. This is consistent with observations in "lethal milk" (lm/lm) mice, which have a truncation mutation in SLC30A4, and present with not only low milk Zn concentration, but also smaller mammary glands, decreased milk volume, and lactation failure by lactation day 2...
January 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/26293594/exome-sequencing-of-slc30a2-identifies-novel-loss-and-gain-of-function-variants-associated-with-breast-cell-dysfunction
#9
Samina Alam, Stephen R Hennigar, Carla Gallagher, David I Soybel, Shannon L Kelleher
The zinc (Zn) transporter ZnT2 (SLC30A2) is expressed in specialized secretory cells including breast, pancreas and prostate, and imports Zn into mitochondria and vesicles. Mutations in SLC30A2 substantially reduce milk Zn concentration ([Zn]) and cause severe Zn deficiency in exclusively breastfed infants. Recent studies show that ZnT2-null mice have low milk [Zn], in addition to profound defects in mammary gland function during lactation. Here, we used breast milk [Zn] to identify novel non-synonymous ZnT2 variants in a population of lactating women...
December 2015: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/25851903/essential-role-for-zinc-transporter-2-znt2-mediated-zinc-transport-in-mammary-gland-development-and-function-during-lactation
#10
Sooyeon Lee, Stephen R Hennigar, Samina Alam, Keigo Nishida, Shannon L Kelleher
The zinc transporter ZnT2 (SLC30A2) imports zinc into vesicles in secreting mammary epithelial cells (MECs) and is critical for zinc efflux into milk during lactation. Recent studies show that ZnT2 also imports zinc into mitochondria and is expressed in the non-lactating mammary gland and non-secreting MECs, highlighting the importance of ZnT2 in general mammary gland biology. In this study we used nulliparous and lactating ZnT2-null mice and characterized the consequences on mammary gland development, function during lactation, and milk composition...
May 22, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25808614/tnf%C3%AE-post-translationally-targets-znt2-to-accumulate-zinc-in-lysosomes
#11
Stephen R Hennigar, Shannon L Kelleher
Mammary epithelial cells undergo widespread lysosomal-mediated cell death (LCD) during early mammary gland involution. Recently, we demonstrated that tumor necrosis factor-α (TNFα), a cytokine released during early involution, redistributes the zinc (Zn) transporter ZnT2 to accumulate Zn in lysosomes and activate LCD and involution. The objective of this study is to determine how TNFα retargets ZnT2 to lysosomes. We tested the hypothesis that TNFα signaling dephosphorylates ZnT2 to uncover a highly conserved dileucine motif (L294L) in the C-terminus of ZnT2, allowing adaptor protein complex-3 (AP-3) to bind and traffic ZnT2 to lysosomes...
October 2015: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/25657003/heterodimerization-altered-subcellular-localization-and-function-of-multiple-zinc-transporters-in-viable-cells-using-bimolecular-fluorescence-complementation
#12
Yarden Golan, Bluma Berman, Yehuda G Assaraf
Zinc plays a crucial role in numerous key physiological functions. Zinc transporters (ZnTs) mediate zinc efflux and compartmentalization in intracellular organelles; thus, ZnTs play a central role in zinc homeostasis. We have recently shown the in situ dimerization and function of multiple normal and mutant ZnTs using bimolecular fluorescence complementation (BiFC). Prompted by these findings, we here uncovered the heterodimerization, altered subcellular localization, and function of multiple ZnTs in live cells using this sensitive BiFC technique...
April 3, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25620235/znt2-is-a-critical-mediator-of-lysosomal-mediated-cell-death-during-early-mammary-gland-involution
#13
Stephen R Hennigar, Young Ah Seo, Supriya Sharma, David I Soybel, Shannon L Kelleher
Mammary gland involution is the most dramatic example of physiological cell death. It occurs through an initial phase of lysosomal-mediated cell death (LCD) followed by mitochondrial-mediated apoptosis. Zinc (Zn) activates both LCD and apoptosis in vitro. The Zn transporter ZnT2 imports Zn into vesicles and mitochondria and ZnT2-overexpression activates cell death in mammary epithelial cells (MECs). We tested the hypothesis that ZnT2-mediated Zn transport is critical for mammary gland involution in mice. Following weaning, ZnT2 abundance increased in lysosomes and mitochondria, which paralleled Zn accumulation in each of these organelles...
2015: Scientific Reports
https://www.readbyqxmd.com/read/25618524/coordinative-modulation-of-human-zinc-transporter-2-gene-expression-through-active-and-suppressive-regulators
#14
Yu-Ju Lu, Ya-Chuan Liu, Meng-Chieh Lin, Yi-Ting Chen, Lih-Yuan Lin
Zinc transporter 2 (ZnT2) is one of the cellular factors responsible for Zn homeostasis. Upon Zn overload, ZnT2 reduces cellular Zn by transporting it into excretory vesicles. We investigated the molecular mechanism that regulates human ZnT2 (hZnT2) gene expression. Zn induces hZnT2 expression in dose- and time-dependent manners. Overexpression of metal-responsive transcription factor 1 (MTF-1) increases hZnT2 transcription, whereas depletion of MTF-1 reduces hZnT2 expression. There are five putative metal response elements (MREs) within 1kb upstream of the hZnT2 gene...
April 2015: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/25468189/genetic-causes-and-gene%C3%A2-nutrient-interactions-in-mammalian-zinc-deficiencies-acrodermatitis-enteropathica-and-transient-neonatal-zinc-deficiency-as-examples
#15
REVIEW
Shakhenabat Kasana, Jamila Din, Wolfgang Maret
Discovering genetic causes of zinc deficiency has been a remarkable scientific journey. It started with the description of a rare skin disease, its treatment with various agents, the successful therapy with zinc, and the identification of mutations in a zinc transporter causing the disease. The journey continues with defining the molecular and cellular pathways that lead to the symptoms caused by zinc deficiency. Remarkably, at least two zinc transporters from separate protein families are now known to be involved in the genetics of zinc deficiency...
January 2015: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/25214972/autophagy-inhibitor-3-methyladenine-regulates-the-expression-of-lc3-beclin-1-and-znts-in-rat-cerebral-cortex-following-recurrent-neonatal-seizures
#16
Hong Ni, Yong Gong, Jian-Zhen Yan, Le-Ling Zhang
BACKGROUND: Autophagy is a homeostatic process for intracellular recycling of bulk proteins and aging organelles. Increased autophagy has now been reported in experimental models of traumatic brain injury, stroke and excitotoxicity, and in patients with Alzheimer's disease and critical illness. The role of autophagy in developmental epilepsy, however, is unknown. The present study was to investigate the effects of recurrent neonatal seizure, in the presence and absence of autophagy inhibitor 3-methyladenine (3-MA), on the acute phase gene expression of ZnTs, LC3 and Beclin-1 in rat cerebral cortex and the interaction among them...
2010: World Journal of Emergency Medicine
https://www.readbyqxmd.com/read/25016022/prolactin-prl-stimulated-ubiquitination-of-znt2-mediates-a-transient-increase-in-zinc-secretion-followed-by-znt2-degradation-in-mammary-epithelial-cells
#17
Young Ah Seo, Sooyeon Lee, Stephen R Hennigar, Shannon L Kelleher
The zinc transporter ZnT2 imports zinc into secretory vesicles and regulates zinc export from the mammary epithelial cell. Mutations in ZnT2 substantially impair zinc secretion into milk. The lactogenic hormone prolactin (PRL) transcriptionally increases ZnT2 expression through the Jak2/STAT5 signaling pathway, increasing zinc accumulation in secretory vesicles and zinc secretion. Herein, we report that PRL post-translationally stimulated ZnT2 ubiquitination, which altered ZnT2 trafficking and augmented vesicular zinc accumulation and secretion from mammary epithelial cells in a transient manner...
August 22, 2014: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/24451381/in-situ-dimerization-of-multiple-wild-type-and-mutant-zinc-transporters-in-live-cells-using-bimolecular-fluorescence-complementation
#18
Inbal Lasry, Yarden Golan, Bluma Berman, Noy Amram, Fabian Glaser, Yehuda G Assaraf
Zinc transporters (ZnTs) facilitate zinc efflux and zinc compartmentalization, thereby playing a key role in multiple physiological processes and pathological disorders, presumed to be modulated by transporter dimerization. We recently proposed that ZnT2 homodimerization is the underlying basis for the dominant negative effect of a novel heterozygous G87R mutation identified in women producing zinc-deficient milk. To provide direct visual evidence for the in situ dimerization and function of multiple normal and mutant ZnTs, we applied here the bimolecular fluorescence complementation (BiFC) technique, which enables direct visualization of specific protein-protein interactions...
March 14, 2014: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/24333596/prolactin-receptor-attenuation-induces-zinc-pool-redistribution-through-znt2-and-decreases-invasion-in-mda-mb-453-breast-cancer-cells
#19
Zeynep Bostanci, Samina Alam, David I Soybel, Shannon L Kelleher
Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER-) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy...
February 15, 2014: Experimental Cell Research
https://www.readbyqxmd.com/read/24311739/upregulation-of-zinc-transporter-2-in-the-blood-csf-barrier-following-lead-exposure
#20
Xue Fu, Andrew Zeng, Wei Zheng, Yansheng Du
Zinc (Zn) is an essential element for normal brain function; an abnormal Zn homeostasis in brain and the cerebrospinal fluid (CSF) has been implied in the etiology of Alzheimer's disease (AD). However, the mechanisms that regulate Zn transport in the blood-brain interface remain unknown. This study was designed to investigate Zn transport by the blood-CSF barrier (BCB) in the choroid plexus, with a particular focus on Zn transporter-2 (ZnT2), and to understand if lead (Pb) accumulation in the choroid plexus disturbed the Zn regulatory function in the BCB...
February 2014: Experimental Biology and Medicine
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