Histone deacetylase inhibitor restores surfactant protein-C expression in alveolar-epithelial type II cells and attenuates bleomycin-induced pulmonary fibrosisin vivo

2015 ◽  
Vol 41 (8) ◽  
pp. 422-434 ◽  
Author(s):  
Chiharu Ota ◽  
Mitsuhiro Yamada ◽  
Naoya Fujino ◽  
Hozumi Motohashi ◽  
Yukiko Tando ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Protein C ◽  
Surfactant Protein ◽  
Type Ii Cells ◽  
Type Ii ◽  
Surfactant Protein C ◽  
Alveolar Epithelial ◽  
Deacetylase Inhibitor

Autophagy regulates hyperoxia-induced intracellular accumulation of surfactant protein C in alveolar type II cells

2015 ◽  
Vol 408 (1-2) ◽  
pp. 181-189 ◽  
Author(s):  
Liang Zhang ◽  
Shuang Zhao ◽  
Li-Jie Yuan ◽  
Hong-Min Wu ◽  
Hong Jiang ◽  
...  
Keyword(s):  
Protein C ◽  
Surfactant Protein ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Intracellular Accumulation ◽  
Alveolar Type Ii Cells ◽  
Surfactant Protein C

Uptake of pulmonary surfactant protein C into adult rat lung lamellar bodies

1993 ◽  
Vol 74 (3) ◽  
pp. 1005-1011 ◽  
Author(s):  
R. A. Pinto ◽  
J. R. Wright ◽  
D. Lesikar ◽  
B. J. Benson ◽  
J. A. Clements
Keyword(s):  
Protein C ◽  
Lamellar Body ◽  
Surfactant Protein ◽  
Type Ii Cells ◽  
Type Ii ◽  
Lamellar Bodies ◽  
Adult Rats ◽  
Alveolar Air ◽  
Surfactant Protein C ◽  
Air Space

Previous studies have provided evidence that a large proportion of secreted surfactant lipids is taken up from the alveolar air space by type II cells, incorporated into lamellar bodies, and resecreted. Our goal was to characterize the clearance of exogenously administered recombinant surfactant protein C (SP-C) and to determine if SP-C is taken up by type II cells and incorporated into lamellar bodies. SP-C was radiolabeled by alkylation with [3H]iodoacetic acid and retained its ability to enhance phospholipid adsorption to an air-liquid interface. A mixture of 100 micrograms phospholipid radiolabeled with [14C]dipalmitoylphosphatidylcholine and 10 micrograms SP-C was instilled into the lungs of spontaneously breathing anesthetized adult rats. At later times, the lungs were lavaged and subcellular organelles were isolated. The radioactivity of both phospholipids and SP-C (expressed as disintegrations per minute per microgram phospholipid) in lamellar body fractions increased up to 4 h postinstillation and began to decline after approximately 4 h. The results of this study suggest that SP-C and dipalmitoylphosphatidylcholine are taken up promptly from the alveolar air space and are incorporated into lamellar bodies with time courses that do not differ greatly.

Synthesis and processing of hydrophobic surfactant protein C by isolated rat type II cells

1995 ◽  
Vol 269 (6) ◽  
pp. L744-L753 ◽  
Author(s):  
M. F. Beers ◽  
C. Lomax
Keyword(s):  
Protein C ◽  
Brefeldin A ◽  
Surfactant Protein ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Metabolic Labeling ◽  
Type Ii ◽  
Surfactant Protein C ◽  
Adult Rat ◽  
The Media

Surfactant protein C (SP-C) is a 3.7-kDa hydrophobic peptide isolated from organic extracts of pulmonary surfactant which is secreted by alveolar type II cells after synthesis and posttranslational processing of a 21-kDa proSP-C peptide (SP-C21). Previously characterized epitope-specific proSP-C antisera were used to study early proteolytic steps of proSP-C processing by adult rat type II cells. Western blotting and immunocytochemistry using anti-NPROSP-C (epitope = Met10-Glu23) each demonstrated marked attenuation of proSP-C protein expression by culture on plastic. Processing was therefore studied by metabolic labeling of freshly isolated type II cells maintained in suspension in serum-free media. With the use of anti-NPROSP-C, immunoprecipitation of cell lysates continuously labeled for 4 h with [35S]methionine demonstrated radiolabeled bands of M(r) 21, 16, and 10-6,000 while anti-CTERMSP-C (epitope = Ser149-Ser166) failed to detect 35S-bands of M(r) < 16,000. Pulse-chase studies demonstrated synthesis of 35S-proSP-C21 with a time-dependent dependent appearance of 16-kDa and 10- to 6-kDa forms which was blocked by addition of brefeldin A. SP-C precursors were not detected in the media. Quantitative analysis of the major bands by direct beta-counting indicated a precursor-product relationship between SP-C21 and SP-C16. These results demonstrate the utility of freshly isolated type II cells for characterization of SP-C synthetic pathways and show that early proSP-C processing events include synthesis of a 21-kDa primary translation product followed by extensive intracellular proteolysis of the proSP-C COOH-terminal in subcellular compartments of type II cells which are distal to the trans-Golgi network.

Surfactant protein C in fetal and ventilated preterm rabbit lungs

1999 ◽  
Vol 277 (6) ◽  
pp. L1104-L1108 ◽  
Author(s):  
Gary F. Ross ◽  
Machiko Ikegami ◽  
Wolfram Steinhilber ◽  
Alan H. Jobe
Keyword(s):  
Protein C ◽  
Surfactant Protein ◽  
Type Ii Cells ◽  
Mrna Levels ◽  
Type Ii ◽  
Surfactant Protein C ◽  
Mature Type ◽  
Alveolar Surfactant ◽  
Surfactant Lipid ◽  
Molar Percent

The developing lung contains surfactant protein (SP) C mRNA levels comparable to term values before mature type II cells and alveolar surfactant lipids are detectable. Estimates of the amount of mature SP-C in the alveolar lavages of preterm lungs are not available. We used an antibody to a recombinant human SP-C to measure the amount of SP-C in alveolar lavages of preterm fetal rabbits, ventilated preterm rabbits, and term rabbits. The amounts of SP-C were compared with the amounts of saturated phosphatidylcholine (Sat PC). Median Sat PC amounts increased about 680-fold, and median SP-C values increased by over 5,000-fold in alveolar washes from 27 days gestation to term. There was no increase in Sat PC or SP-C with ventilation at 27 and 28 days gestation, but ventilation increased both Sat PC and SP-C at 29 days gestation. The molar percent of SP-C relative to Sat PC also increased with gestational age and with ventilation at 29 days gestation. proSP-C was abundant in a membrane fraction from lung tissue at 27 and 28 days gestation when minimal mature SP-C was detected in alveolar washes. At 29 days and at term, proSP-C decreased in membrane fractions. The preterm lung that is surfactant lipid deficient is also severely deficient in mature SP-C.

Posttranslational processing of surfactant protein C in rat type II cells

1995 ◽  
Vol 269 (6) ◽  
pp. L727-L733 ◽  
Author(s):  
D. K. Vorbroker ◽  
W. F. Voorhout ◽  
T. E. Weaver ◽  
J. A. Whitsett
Keyword(s):  
Protein C ◽  
Surfactant Protein ◽  
Proteolytic Processing ◽  
Proteinase K ◽  
Multivesicular Bodies ◽  
Type Ii Cells ◽  
Type Ii ◽  
Lamellar Bodies ◽  
Surfactant Protein C

Pulmonary surfactant consists of phospholipids and proteins that form a stable monolayer at the surface of the alveoli to prevent lung collapse. Surfactant protein C (SP-C) is a hydrophobic 4-kDa palmitoylated protein derived from a 21-kDa precursor. We determined the membrane insertion, proteolytic processing, and subcellular location of 21-kDa proSP-C. In vitro, proSP-C associated with canine microsomes, and the NH2-terminal of proSP-C was protected from digestion with proteinase K, suggesting that proSP-C was inserted in a type III transmembrane configuration. Treatment of freshly isolated rat type II cells with cerulenin blocked acylation of the 21-kDa precursor. Pulse-chase labeling of type II cells demonstrated proSP-C processing intermediates of 19, 16, and 13 kDa that contained the NH2-terminal of proSP-C. Proteolytic processing of proSP-C was inhibited by incubation at 20 degrees C, suggesting that processing of proSP-C begins in a late Golgi or post-Golgi compartment. Immunogold labeling of rat lung with an antiserum to the NH2-terminal of proSP-C identified proSP-C in the trans-Golgi and multivesicular bodies but not in lamellar bodies. These findings suggest that proSP-C processing takes place in the trans-Golgi and multivesicular bodies before SP-C is incorporated into lamellar bodies.

Association of surfactant protein C with isolated alveolar type II cells

1995 ◽  
Vol 1255 (1) ◽  
pp. 16-22 ◽  
Author(s):  
Ricardo A. Pinto ◽  
Samuel Hawgood ◽  
John A. Clements ◽  
Bradley J. Benson ◽  
Asha Naidu ◽  
...  
Keyword(s):  
Protein C ◽  
Surfactant Protein ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Surfactant Protein C

scholarly journals A Tiny Change Makes a Big Difference in the Anti-Parasitic Activities of an HDAC Inhibitor

2019 ◽  
Vol 20 (12) ◽  
pp. 2973 ◽  
Author(s):  
Corinne Loeuillet ◽  
Bastien Touquet ◽  
Jean François Guichou ◽  
Gilles Labesse ◽  
Denis Sereno
Keyword(s):  
Toxoplasma Gondii ◽  
Histone Deacetylase ◽  
Hdac Inhibitor ◽  
In Silico ◽  
Histone Deacetylase Inhibitor ◽  
Type Ii ◽  
Deacetylase Inhibitor ◽  
In Silico Modeling ◽  
High Conservation ◽  
Methyl Benzene

We previously synthesized an hydroxamate derivative (N-hydroxy-4-[2-(3- methoxyphenyl)acetamido]benzamide) named 363 with potent anti-Toxoplasma gondii activity and histone deacetylase inhibitor (HDACi) effects. Here we show that 1-N-hydroxy-4-N- [(2-methoxyphenyl)methyl]benzene-1,4-dicarboxamide, a 363 isomer, does not have antiparasitic potency and has a 13-fold decrease in HDACi activity. The in silico modeling of T. gondii HDACs of the type II strain discloses identity varying from 25% to 62% on more than 250 residues for S8EP32_TOXG and A0A125YPH4_TOXGM. We observed a high conservation degree with the human HDAC2 (53% and 64% identity, respectively) and a moderate one with the human HDAC8 (30–40%). Two other TgHDACs, S8F6L4_TOXGM and S8GEI3_TOXGM, were identified as displaying a higher similarity with some bacterial orthologs (~35%) than with the human enzymes (~25%). The docking in parallel of the two compounds on the models generated allowed us to gain insights on the docking of these hydroxamate derivatives that guide their specificity and potency against T. gondii histone deacetylase. This information would constitute the rationale from which more specific derivatives can be synthetized.

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