Role of Monosaccharide Transport Proteins in Carbohydrate Assimilation, Distribution, Metabolism, and Homeostasis

AbstractCholesterol has long been suspected of influencing hair biology, with dysregulated homeostasis implicated in several disorders of hair growth and cycling. Cholesterol transport proteins play a vital role in the control of cellular cholesterol levels and compartmentalisation. This research aimed to determine the cellular localisation, transport capability and regulatory control of cholesterol transport proteins across the hair cycle. Immunofluorescence microscopy in human hair follicle sections revealed differential expression of ATP-binding cassette (ABC) transporters across the hair cycle. Cholesterol transporter expression (ABCA1, ABCG1, ABCA5 and SCARB1) reduced as hair follicles transitioned from growth to regression. Staining for free cholesterol (filipin) revealed prominent cholesterol striations within the basement membrane of the hair bulb. Liver X receptor agonism demonstrated active regulation of ABCA1 and ABCG1, but not ABCA5 or SCARB1 in human hair follicles and primary keratinocytes. These results demonstrate the capacity of human hair follicles for cholesterol transport and trafficking. Future studies examining the role of cholesterol transport across the hair cycle may shed light on the role of lipid homeostasis in human hair disorders.

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Abstract 16440: Cu Transporter ATP7A Protects Against Fibrosis Through Limiting Endothelial to Mesenchymal Transition

Circulation ◽

10.1161/circ.130.suppl_2.16440 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Seock-Won Youn ◽

Sudhahar Varadarajan ◽

Archita Das ◽

Ronald D McKinney ◽

Tohru Fukai ◽

...

Keyword(s):

Transcription Factor ◽

Inflammatory Diseases ◽

Shape Change ◽

Atherosclerotic Lesion ◽

Transport Proteins ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Endothelial To Mesenchymal Transition

Background: Endothelial to mesenchymal transition (EndMT) is induced by inflammation and contributes to fibrosis; however, underlying mechanism is poorly understood. Cu plays an important role in physiological processes and pathophysiologies associated with inflammatory diseases. Since excess Cu is toxic, bioavailability of Cu is tightly controlled by Cu exporter ATP7A, which obtains Cu via Cu chaperone, Atox1, and exclude Cu. We reported that Atox1 also functions as a Cu dependent transcription factor. However, role of Cu transport proteins in EndMT is entirely unknown.[[Unable to Display Character:  ]] Results: Here we show that TNFα stimulation for 24hr in HUVEC significantly decreased ATP7A protein (80%) and increased intracellular Cu and Atox1 in nucleus, which was associated with shape change forming EndMT. ATP7A depletion with shRNA in EC significantly reduced EC markers (VE-cadherin and VEGFR2) and increased mesenchymal markers (αSMA, Calponin, SM22α, Collagen I/II). ATP7A siRNA also increased intracellular Cu and nuclear Atox1. These ATP7A knockdown-induced phenotype changes were inhibited by Cu chelators BCS and TTM. Mechanistically, microarray and qPCR based screening revealed that ATP7A knockdown in EC significantly increased miR21 (2.5 fold) and miR125b (1.5 fold) which induce EndMT in a Cu-dependent manner. Of note, promoters of both miR21 and miR125b have Cu dependent transcription factor Atox1 binding sites. Consistent with this, overexpression of Atox1 increased miR21 and miR125b expression as well as promoted EndMT. In vivo, ATP7A mutant (ATP7Amut) mice with reduced Cu export function showed impaired blood flow recovery and reduced arteriogenesis while increased αSMA+ cells and fibrosis in capillary network after ischemic injury. Moreover, ATP7Amut mice crossed with ApoE-/- mice with high fat diet (HFD) induced robust fibrosis and enhanced atherosclerotic lesion vs ApoE-/-/HFD mice.[[Unable to Display Character:  ]] Conclusions: ATP7A protects against fibrosis by preventing EndMT via nuclear Atox1-mediated upregulation of miR21 and miR125b which induce EndMT, in Cu dependent manner. These findings provide the foundation for novel protective role of Cu transport proteins against EndMT- and fibrosis-mediated cardiovascular diseases.

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Sorting Mechanisms for MicroRNAs into Extracellular Vesicles and Their Associated Diseases

Cells ◽

10.3390/cells9041044 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1044 ◽

Cited By ~ 19

Author(s):

Michael Groot ◽

Heedoo Lee

Keyword(s):

Extracellular Vesicles ◽

Potential Role ◽

Rna Binding ◽

Rna Binding Proteins ◽

Transport Proteins ◽

Caveolin 1 ◽

Argonaute 2 ◽

Disease States ◽

Mirna Content

Extracellular vesicles (EV) are secretory membranous elements used by cells to transport proteins, lipids, mRNAs, and microRNAs (miRNAs). While their existence has been known for many years, only recently has research begun to identify their function in intercellular communication and gene regulation. Importantly, cells have the ability to selectively sort miRNA into EVs for secretion to nearby or distant targets. These mechanisms broadly include RNA-binding proteins such as hnRNPA2B1 and Argonaute-2, but also membranous proteins involved in EV biogenesis such as Caveolin-1 and Neural Sphingomyelinase 2. Moreover, certain disease states have also identified dysregulated EV-miRNA content, shedding light on the potential role of selective sorting in pathogenesis. These pathologies include chronic lung disease, immune response, neuroinflammation, diabetes mellitus, cancer, and heart disease. In this review, we will overview the mechanisms whereby cells selectively sort miRNA into EVs and also outline disease states where EV-miRNAs become dysregulated.

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Estrogen Regulates Duodenal Calcium Absorption Through Differential Role of Estrogen Receptor on Calcium Transport Proteins

Digestive Diseases and Sciences ◽

10.1007/s10620-020-06076-x ◽

2020 ◽

Vol 65 (12) ◽

pp. 3502-3513 ◽

Cited By ~ 2

Author(s):

Xubiao Nie ◽

Hai Jin ◽

Guorong Wen ◽

Jingyu Xu ◽

Jiaxing An ◽

...

Keyword(s):

Estrogen Receptor ◽

Calcium Transport ◽

Calcium Absorption ◽

Transport Proteins

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Role of Four Calcium Transport Proteins, Encoded bynca-1,nca-2,nca-3, andcax, in Maintaining Intracellular Calcium Levels in Neurospora crassa

Eukaryotic Cell ◽

10.1128/ec.00239-10 ◽

2011 ◽

Vol 10 (5) ◽

pp. 654-661 ◽

Cited By ~ 28

Author(s):

Barry J. Bowman ◽

Stephen Abreu ◽

Emilio Margolles-Clark ◽

Marija Draskovic ◽

Emma Jean Bowman

Keyword(s):

Neurospora Crassa ◽

Calcium Transport ◽

High Speed ◽

Transport Proteins ◽

Cell Fractionation ◽

Animal Cells ◽

Normal Medium ◽

Content Type ◽

Cell Fractions

ABSTRACTWe have examined the distribution of calcium inNeurospora crassaand investigated the role of four predicted calcium transport proteins. The results of cell fractionation experiments showed 4% of cellular calcium in mitochondria, approximately 11% in a dense vacuolar fraction, 40% in an insoluble form that copurifies with microsomes, and 40% in a high-speed supernatant, presumably from large vacuoles that had broken. Strains lacking NCA-1, a SERCA-type Ca2+-ATPase, or NCA-3, a PMC-type Ca2+-ATPase, had no obvious defects in growth or distribution of calcium. A strain lacking NCA-2, which is also a PMC-type Ca2+-ATPase, grew slowly in normal medium and was unable to grow in high concentrations of calcium tolerated by the wild type. Furthermore, when grown in normal concentrations of calcium (0.68 mM), this strain accumulated 4- to 10-fold more calcium than other strains, elevated in all cell fractions. The data suggest that NCA-2 functions in the plasma membrane to pump calcium out of the cell. In this way, it resembles the PMC-type enzymes of animal cells, not the Pmc1p enzyme inSaccharomyces cerevisiaethat resides in the vacuole. Strains lacking thecaxgene, which encodes a Ca2+/H+exchange protein in vacuolar membranes, accumulate very little calcium in the dense vacuolar fraction but have normal levels of calcium in other fractions. Thecaxknockout strain has no other observable phenotypes. These data suggest that “the vacuole” is heterogeneous and that the dense vacuolar fraction contains an organelle that is dependent upon the CAX transporter for accumulation of calcium, while other components of the vacuolar system have multiple calcium transporters.

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Equine Drug Transporters: A Mini-Review and Veterinary Perspective

Pharmaceutics ◽

10.3390/pharmaceutics12111064 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1064

Author(s):

Brielle Rosa

Keyword(s):

Drug Transport ◽

Drug Disposition ◽

Drug Transporters ◽

Transport Proteins ◽

Pharmacokinetic Parameters ◽

Transporter Protein ◽

Drug Pharmacokinetic ◽

Species Specific ◽

And Function

Xenobiotic transport proteins play an important role in determining drug disposition and pharmacokinetics. Our understanding of the role of these important proteins in humans and pre-clinical animal species has increased substantially over the past few decades, and has had an important impact on human medicine; however, veterinary medicine has not benefitted from the same quantity of research into drug transporters in species of veterinary interest. Differences in transporter expression cause difficulties in extrapolation of drug pharmacokinetic parameters between species, and lack of knowledge of species-specific transporter distribution and function can lead to drug–drug interactions and adverse effects. Horses are one species in which little is known about drug transport and transporter protein expression. The purpose of this mini-review is to stimulate interest in equine drug transport proteins and comparative transporter physiology.

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