Poly(ADP-ribose) Polymerase 1 Represses Liver X Receptor-mediated ABCA1 Expression and Cholesterol Efflux in Macrophages

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.

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Interferon‐γ decreases ATP‐binding cassette subfamily G member 1‐mediated cholesterol efflux through small ubiquitin‐like modifier/ubiquitin‐dependent liver X receptor‐α degradation in macrophages

Biotechnology and Applied Biochemistry ◽

10.1002/bab.2063 ◽

2020 ◽

Author(s):

Mengya Dong ◽

Yan Zhang ◽

Chenbo Xu ◽

Chen Wang ◽

Mengping Liu ◽

...

Keyword(s):

Cholesterol Efflux ◽

Interferon Γ ◽

Liver X Receptor ◽

Atp Binding ◽

Liver X Receptor Α ◽

Atp Binding Cassette

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Differential regulation of ABCA1 expression and cholesterol efflux during adipose differentiation

Atherosclerosis Supplements ◽

10.1016/s1567-5688(02)80391-9 ◽

2002 ◽

Vol 3 (2) ◽

pp. 150

Keyword(s):

Cholesterol Efflux ◽

Differential Regulation ◽

Abca1 Expression ◽

Adipose Differentiation

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2P-0439 Effect of HMG CoA reductase inhibitor (statin) on ABCA1 expression and HDL-induced cholesterol efflux in macrophages

Atherosclerosis Supplements ◽

10.1016/s1567-5688(03)90581-2 ◽

2003 ◽

Vol 4 (2) ◽

pp. 135-136

Author(s):

H. Yoshida ◽

N. Tada

Keyword(s):

Cholesterol Efflux ◽

Reductase Inhibitor ◽

Hmg Coa Reductase ◽

Abca1 Expression ◽

Hmg Coa Reductase Inhibitor ◽

Coa Reductase

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Carvedilol Ameliorates Experimental Atherosclerosis by Regulating Cholesterol Efflux and Exosome Functions

International Journal of Molecular Sciences ◽

10.3390/ijms20205202 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5202 ◽

Cited By ~ 2

Author(s):

Chen ◽

Tsui ◽

Chuang ◽

Chiang ◽

Chen ◽

...

Keyword(s):

Cholesterol Efflux ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Nuclear Factor Κb ◽

Experimental Atherosclerosis ◽

Atherosclerotic Cardiovascular Disease ◽

Beneficial Effects ◽

Abca1 Expression ◽

Density Lipoprotein Receptor ◽

And Function

Carvedilol (Cav), a nonselective β-blocker with α1 adrenoceptor blocking effect, has been used as a standard therapy for coronary artery disease. This study investigated the effects of Cav on exosome expression and function, ATP-binding cassette transporter A1 (ABCA1) expression, and cholesterol efflux that are relevant to the process of atherosclerosis. Human monocytic (THP-1) cell line and human hepatic (Huh-7) cells were treated with Cav, and cholesterol efflux was measured. Exosomes from cell culture medium or mice serum were isolated using glycan-coated recognition beads. Low-density lipoprotein receptor knockout (ldlr−/−) mice were fed with high-fat diet and treated with Cav. Cav accentuated cholesterol efflux and enhanced the expressions of ABCA1 protein and mRNA in both THP-1 and Huh-7 cells. In addition, Cav increased expression and function of exosomal ABCA1 in THP-1 macrophage exosomes. The mechanisms were associated with inhibition of nuclear factor-κB (NF-κB) and protein kinase B (Akt). In hypercholesterolemic ldlr−/− mice, Cav enhanced serum exosomal ABCA1 expression and suppressed atherosclerosis by inhibiting lipid deposition and macrophage accumulation. Cav halts atherosclerosis by enhancing cholesterol efflux and increasing ABCA1 expression in macrophages and in exosomes, possibly through NF-κB and Akt signaling, which provides mechanistic insights regarding the beneficial effects of Cav on atherosclerotic cardiovascular disease.

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LncRNA kcnq1ot1 promotes lipid accumulation and accelerates atherosclerosis via functioning as a ceRNA through the miR-452-3p/HDAC3/ABCA1 axis

Cell Death and Disease ◽

10.1038/s41419-020-03263-6 ◽

2020 ◽

Vol 11 (12) ◽

Author(s):

Xiao-Hua Yu ◽

Wen-Yi Deng ◽

Jiao-Jiao Chen ◽

Xiao-Dan Xu ◽

Xian-Xia Liu ◽

...

Keyword(s):

Cardiovascular Disease ◽

Atherosclerotic Plaque ◽

Lipid Accumulation ◽

Cholesterol Efflux ◽

Underlying Mechanism ◽

Western Diet ◽

Plaque Area ◽

Abca1 Expression ◽

Potential Contributor ◽

Mouse Aorta

AbstractKcnq1 overlapping transcript 1 (kcnq1ot1), an imprinted antisense lncRNA in the kcnq1 locus, acts as a potential contributor to cardiovascular disease, but its role in atherosclerosis remains unknown. The aim of this study was to explore the effects of kcnq1ot1 on atherogenesis and the underlying mechanism. Our results showed that kcnq1ot1 expression was significantly increased in mouse aorta with atherosclerosis and lipid-loaded macrophages. Lentivirus-mediated kcnq1ot1 overexpression markedly increased atherosclerotic plaque area and decreased plasma HDL-C levels and RCT efficiency in apoE−/− mice fed a Western diet. Upregulation of kcnq1ot1 also reduced the expression of miR-452-3p and ABCA1 but increased HDAC3 levels in mouse aorta and THP-1 macrophages. Accordingly, kcnq1ot1 overexpression inhibited cholesterol efflux and promoted lipid accumulation in THP-1 macrophages. In contrast, kcnq1ot1 knockdown protected against atherosclerosis in apoE−/− mice and suppressed lipid accumulation in THP-1 macrophages. Mechanistically, kcnq1ot1 enhanced HDAC3 expression by competitively binding to miR-452-3p, thereby inhibiting ABCA1 expression and subsequent cholesterol efflux. Taken together, these findings suggest that kcnq1ot1 promotes macrophage lipid accumulation and accelerates the development of atherosclerosis through the miR-452-3p/HDAC3/ABCA1 pathway.

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