Alteration of the Pulmonary Surfactant System in Full-Term Infants with Hereditary ABCA3 Deficiency

Brasch, Frank; Schimanski, Sven; Mühlfeld, Christian; Barlage, Stefan; Langmann, Thomas; Aslanidis, Charalampos; Boettcher, Alfred; Dada, Ashraf; Schroten, Horst; Mildenberger, Eva; Prueter, Eric; Ballmann, Manfred; Ochs, Matthias; Johnen, Georg; Griese, Matthias; Schmitz, Gerd

doi:10.1164/rccm.200509-1535oc

Cited by 147 publications

(127 citation statements)

References 38 publications

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“…Sequences were aligned to the reference sequence (RefSeq accession NG_029334) using Mutation Surveyor 4.0 (SoftGenetics, State College, PA). ABCA3 and TTF1 were determined as described previously (38,39).…”

Section: Genetic Analysismentioning

confidence: 99%

Surfactant proteins in pediatric interstitial lung disease

et al. 2015

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Section: Genetic Analysismentioning

confidence: 99%

Surfactant proteins in pediatric interstitial lung disease

et al. 2015

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“…Exogenous expression of ABCA3 in cultured cells promotes lipid uptake into intracellular vesicles that generate lamellar body-like vesicles (7,18,21). ABCA3 deficiency in human and mice leads to decreased phosphatidylcholine and phosphatidylglycerol in surfactant, dysgenesis of lamellar bodies, and respiratory distress (1,3,8,11,12,27). Considered together, these results indicate that ABCA3 is an essential lipid transporter in surfactant metabolism.…”

mentioning

confidence: 90%

Aberrant catalytic cycle and impaired lipid transport into intracellular vesicles in ABCA3 mutants associated with nonfatal pediatric interstitial lung disease

Matsumura¹,

Ban²,

Inagaki³

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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However, the mechanisms underlying the less severe phenotype of patients with ABCA3 mutation are unclear. In this study, we characterized ABCA3 mutant proteins identified in pediatric interstitial lung disease (pILD). E292V (intracellular loop 1), E690K (adjacent to Walker B motif in nucleotide binding domain 1), and T1114M (8th putative transmembrane segment) mutant proteins are localized mainly in intracellular vesicle membranes as wild-type protein. Lipid analysis and sucrose gradient fractionation revealed that the transport function of E292V mutant protein is moderately preserved, whereas those of E690K and T1114M mutant proteins are severely impaired. Vanadate-induced nucleotide trapping and photoaffinity labeling of wild-type and mutant proteins using 8-azido-[ 32 P]ATP revealed an aberrant catalytic cycle in these mutant proteins. These results demonstrate the importance of a functional catalytic cycle in lipid transport of ABCA3 and suggest a pathophysiological mechanism of pILD due to ABCA3 mutation.

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“…ABCA1, the best studied of the proteins, is causally linked to Tangier disease and is associated with defective phospholipid and cholesterol transport from intracellular lipid stores to the major amphipathic helical apoprotein of high density lipoprotein, apolipoprotein A-1 (8 -11). ABCA3 mutations cause a form of neonatal respiratory failure that arises from a failure to transport pulmonary phospholipids comprising surfactant from their storage site in the lamellar bodies of alveolar type II cells to the alveolar space (12)(13)(14). This transport process, like the one involving ABCA1, appears to depend on the lipidation of an acceptor amphipathic helical protein, surfactant protein B (15, 16).…”

Section: Harlequin Ichthyosis (Hi)mentioning

confidence: 99%

ABCA12 Maintains the Epidermal Lipid Permeability Barrier by Facilitating Formation of Ceramide Linoleic Esters

Zuo

Zhuang

Han

et al. 2008

Journal of Biological Chemistry

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Harlequin ichthyosis is a congenital scaling syndrome of the skin in which affected infants have epidermal hyperkeratosis and a defective permeability barrier. Mutations in the gene encoding a member of the ABCA transporter family, ABCA12, have been linked to harlequin ichthyosis, but the molecular function of the protein is unknown. To investigate the activity of ABCA12, we generated Abca12 null mice and analyzed the impact on skin function and lipid content. Abca12 ؊/؊ mice are born with a thickened epidermis and die shortly after birth, as water rapidly evaporates from their skin. In vivo skin proliferation measurements suggest a lack of desquamation of the skin cells, rather than enhanced proliferation of basal layer keratinocytes, accounts for the 5-fold thickening of the Abca12 ؊/؊ stratum corneum. Electron microscopy revealed a loss of the lamellar permeability barrier in Abca12 ؊/؊ skin. This was associated with a profound reduction in skin linoleic esters of long-chain -hydroxyceramides and a corresponding increase in their glucosyl ceramide precursors. Because -hydroxyceramides are required for the barrier function of the skin, these results establish that ABCA12 activity is required for the generation of longchain ceramide esters that are essential for the development of normal skin structure and function. Harlequin ichthyosis (HI)2 is the most severe of the congenital, autosomal ichthyoses with affected infants developing large, hard, plate-like scales over all of their epidermal surfaces. Abnormal temperature regulation, enhanced water loss, and bacterial super-infections develop as a consequence of defects in the barrier functions of the skin, making survival through the neonatal period difficult. In recent years, several groups have linked HI, as well as less severe forms of ichthyosis, to mutations in the gene encoding a member of the ABCA family of transporters, ABCA12 (1-7). The A class of ABC transporters consists of at least eleven transporters in humans and mice, several of which are known to play critical roles in human disease. ABCA1, the best studied of the proteins, is causally linked to Tangier disease and is associated with defective phospholipid and cholesterol transport from intracellular lipid stores to the major amphipathic helical apoprotein of high density lipoprotein, apolipoprotein A-1 (8 -11). ABCA3 mutations cause a form of neonatal respiratory failure that arises from a failure to transport pulmonary phospholipids comprising surfactant from their storage site in the lamellar bodies of alveolar type II cells to the alveolar space (12)(13)(14). This transport process, like the one involving ABCA1, appears to depend on the lipidation of an acceptor amphipathic helical protein, surfactant protein B (15, 16). ABCA4 causes Stargadt macular degeneration and visual loss that is associated with a defect in the transport of phosphatidylethanolamine-retinylidene adducts out of retinal pigment epithelial cells (17)(18)(19). The role of any acceptor proteins in this process is unknown. T...

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Alteration of the Pulmonary Surfactant System in Full-Term Infants with Hereditary ABCA3 Deficiency

Cited by 147 publications

References 38 publications

Surfactant proteins in pediatric interstitial lung disease

Surfactant proteins in pediatric interstitial lung disease

Aberrant catalytic cycle and impaired lipid transport into intracellular vesicles in ABCA3 mutants associated with nonfatal pediatric interstitial lung disease

ABCA12 Maintains the Epidermal Lipid Permeability Barrier by Facilitating Formation of Ceramide Linoleic Esters

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