- HDL, ABC Transporters, and Cholesterol Efflux as Therapeutic Targets in Atherosclerosis

2012 ◽  
pp. 185-200
Keyword(s):  
Abc Transporters ◽  
Cholesterol Efflux ◽  
Therapeutic Targets

scholarly journals The ABCA1 blocking agent probucol decreases capacitation in ejaculated dog spermatozoa

2020 ◽  
Vol 62 (1) ◽  
Author(s):  
Sabine Schäfer-Somi ◽  
Sven Budik
Keyword(s):  
Abc Transporters ◽  
Cholesterol Efflux ◽  
Blocking Agent ◽  
Negative Control ◽  
Cholesterol Concentration ◽  
Abca1 Expression ◽  
Healthy Dogs ◽  
Epididymal Spermatozoa ◽  
Phospholipid Transport ◽  
Cholesterol Measurement

Abstract Background The ATP binding cassette (ABC) transporters participate in the cholesterol and phospholipid transport within and through cell membranes of many cells including spermatozoa. Cholesterol efflux is important for capacitation of spermatozoa. ABCA1 expression has been assessed in canine spermatozoa previously but its role in capacitation still has to be determined. The aim of the study was to test whether inhibition of ABCA1 (1) decreases capacitation in ejaculated and epididymal canine sperm samples and (2) decreases cholesterol efflux in the same samples. Twenty-one ejaculates and sperm from 22 epididymal tails were collected from healthy dogs. Motility was measured by CASA and viability assessed after staining with SYBR-14/PI. Samples from ejaculated sperm and sperm from epididymal tails were aliquoted. One part was incubated with the ABCA1 inhibitor probucol, the other served as a negative control. In all samples, capacitation was evaluated by chlortetracyclin (CTC) assay and cholesterol was measured by cholesterol efflux assay and colorimetric enzymatic assay. Results In ejaculated sperm, blockade of ABCA1 with 100 µM of probucol/mL of sample resulted in a significantly higher percentage of uncapacitated and acrosome reacted spermatozoa (P < 0.001 and P = 0.031), capacitation was significantly decreased (35% in probucol samples vs 54.2% in controls, P < 0.001). In probucol inhibited sperm samples from epididymal tails, the percentage of capacitated spermatozoa did not differ between groups but the percentage of acrosome reacted spermatozoa increased significantly (P = 0.014). The cholesterol measurement revealed significantly lower cholesterol concentration in the probucol group when compared to the controls (P = 0.035), however only in ejaculated sperm samples. Conclusions CTC assay and cholesterol measurement revealed significant differences between groups; we conclude that inhibition of ABCA1 significantly decreased capacitation and cholesterol efflux in ejaculated canine spermatozoa. The inhibition was not complete but ABCA1 is supposed to contribute to capacitation in canine ejaculated spermatozoa. ABCA1 is probably not important for capacitation of epididymal spermatozoa but might exert other functions during spermatozoa ripening.

scholarly journals Sulfadiazine resistance inToxoplasma gondii: no involvement of overexpression or polymorphisms in genes of therapeutic targets and ABC transporters

Parasite ◽  
2013 ◽  
Vol 20 ◽  
pp. 19 ◽  
Author(s):  
Christelle Doliwa ◽  
Sandie Escotte-Binet ◽  
Dominique Aubert ◽  
Virginie Sauvage ◽  
Frédéric Velard ◽  
...  
Keyword(s):  
Abc Transporters ◽  
Therapeutic Targets

scholarly journals ABC Transporters: Unvalidated Therapeutic Targets in Cancer and the CNS

2010 ◽  
Vol 10 (8) ◽  
pp. 625-633 ◽  
Author(s):  
Robert W. Robey ◽  
Paul R. Massey ◽  
Laleh Amiri-Kordestani ◽  
Susan E. Bates
Keyword(s):  
Abc Transporters ◽  
Therapeutic Targets

scholarly journals Molecular basis of cholesterol efflux via ABCG subfamily transporters

2021 ◽  
Vol 118 (34) ◽  
pp. e2110483118
Author(s):  
Yingyuan Sun ◽  
Jin Wang ◽  
Tao Long ◽  
Xiaofeng Qi ◽  
Linda Donnelly ◽  
...  
Keyword(s):  
Abc Transporters ◽  
Binding Sites ◽  
Molecular Basis ◽  
Cholesterol Efflux ◽  
Bound States ◽  
High Density Lipoproteins ◽  
Cellular Cholesterol ◽  
Nucleotide Binding Sites ◽  
Cholesterol Levels ◽  
Neutral Sterols

The ABCG1 homodimer (G1) and ABCG5–ABCG8 heterodimer (G5G8), two members of the adenosine triphosphate (ATP)–binding cassette (ABC) transporter G family, are required for maintenance of cellular cholesterol levels. G5G8 mediates secretion of neutral sterols into bile and the gut lumen, whereas G1 transports cholesterol from macrophages to high-density lipoproteins (HDLs). The mechanisms used by G5G8 and G1 to recognize and export sterols remain unclear. Here, we report cryoelectron microscopy (cryo-EM) structures of human G5G8 in sterol-bound and human G1 in cholesterol- and ATP-bound states. Both transporters have a sterol-binding site that is accessible from the cytosolic leaflet. A second site is present midway through the transmembrane domains of G5G8. The Walker A motif of G8 adopts a unique conformation that accounts for the marked asymmetry in ATPase activities between the two nucleotide-binding sites of G5G8. These structures, along with functional validation studies, provide a mechanistic framework for understanding cholesterol efflux via ABC transporters.

scholarly journals HDL, ABC Transporters, and Cholesterol Efflux: Implications for the Treatment of Atherosclerosis

2008 ◽  
Vol 7 (5) ◽  
pp. 365-375 ◽  
Author(s):  
Alan R. Tall ◽  
Laurent Yvan-Charvet ◽  
Naoki Terasaka ◽  
Tamara Pagler ◽  
Nan Wang
Keyword(s):  
Abc Transporters ◽  
Cholesterol Efflux
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