scholarly journals The expression and function of ATP‐binding cassette transporter G1 (ABCG1) is down‐regulated by inflammatory stimuli through the inhibition of peroxisome proliferator‐activated receptor gamma (PPAR gamma) pathway in macrophages

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Ji‐Young Lee ◽  
Young‐Ki Park ◽  
Mark A. Heffley ◽  
Heather E. Rasmussen ◽  
Sarah J. Ehlers
Keyword(s):  
Ppar Gamma ◽  
Atp Binding ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Atp Binding Cassette Transporter ◽  
Inflammatory Stimuli ◽  
And Function ◽  
Atp Binding Cassette

scholarly journals PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer

Oncogene ◽  
2021 ◽  
Vol 40 (13) ◽  
pp. 2355-2366
Author(s):  
Laura C. A. Galbraith ◽  
Ernest Mui ◽  
Colin Nixon ◽  
Ann Hedley ◽  
David Strachan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mitochondrial Biogenesis ◽  
Nuclear Export ◽  
Epithelial To Mesenchymal Transition ◽  
Ppar Gamma ◽  
Peroxisome Proliferator ◽  
Serine Threonine Kinase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mesenchymal Transition ◽  
And Function

AbstractPeroxisome Proliferator-Activated Receptor Gamma (PPARG) is one of the three members of the PPAR family of transcription factors. Besides its roles in adipocyte differentiation and lipid metabolism, we recently demonstrated an association between PPARG and metastasis in prostate cancer. In this study a functional effect of PPARG on AKT serine/threonine kinase 3 (AKT3), which ultimately results in a more aggressive disease phenotype was identified. AKT3 has previously been shown to regulate PPARG co-activator 1 alpha (PGC1α) localisation and function through its action on chromosome maintenance region 1 (CRM1). AKT3 promotes PGC1α localisation to the nucleus through its inhibitory effects on CRM1, a known nuclear export protein. Collectively our results demonstrate how PPARG over-expression drives an increase in AKT3 levels, which in turn has the downstream effect of increasing PGC1α localisation within the nucleus, driving mitochondrial biogenesis. Furthermore, this increase in mitochondrial mass provides higher energetic output in the form of elevated ATP levels which may fuel the progression of the tumour cell through epithelial to mesenchymal transition (EMT) and ultimately metastasis.

scholarly journals Human Lupus Plasma Pro-Atherogenic Effects on Cultured Macrophages Are Not Mitigated by Statin Therapy: A Mechanistic LAPS Substudy

Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 514 ◽  
Author(s):  
Reiss ◽  
Arain ◽  
Kasselman ◽  
Renna ◽  
Zhen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lupus Erythematosus ◽  
Cholesterol Metabolism ◽  
Lipid Lowering ◽  
Cholesterol Transport ◽  
Atp Binding ◽  
Peroxisome Proliferator ◽  
Atherosclerotic Cardiovascular Disease ◽  
Peroxisome Proliferator Activated Receptor ◽  
Atp Binding Cassette

Background and Objectives: Atherosclerotic cardiovascular disease (CVD) remains a major cause of morbidity and mortality in persons with systemic lupus erythematosus (SLE, lupus). Atherosclerosis, which involves interplay between cholesterol metabolism and cellular inflammatory pathways, is primarily treated with statins since statins have lipid-lowering and anti-inflammatory properties. The Lupus Atherosclerosis Prevention Study (LAPS) was designed to investigate the efficacy of statins against CVD in SLE patients. LAPS demonstrated that 2 years of atorvastatin administration did not reduce atherosclerosis progression in lupus patients. In this LAPs substudy, we use cultured macrophages to explore the atherogenic properties of plasma from LAPS subjects to explain the mechanistic rationale for the inability of statins to reduce CVD in lupus. Materials and Methods: THP-1 differentiated macrophages were treated for 18 h with 10% SLE patient plasma obtained pre- and post-atorvastatin therapy or placebo. Gene expression of the following cholesterol transport genes was measured by qRT-PCR. For efflux—ATP binding cassette transporter (ABC)A1 and ABCG1, 27-hydroxylase, peroxisome proliferator-activated receptor (PPAR)γ, and liver X receptor (LXR)α; and for influx—cluster of differentiation 36 (CD36) and scavenger receptor (ScR)A1. Results: Macrophages exposed to plasma from both statin-treated and placebo-treated groups showed a significant decrease in cholesterol efflux proteins ATP binding cassette (ABC) transporters A1 and ABCG1, an increase in 27-hydroxylase, an increase in the LDL receptor and a decrease in intracellular free cholesterol. No change in influx receptors ScRA1 and CD36, nor nuclear proteins LXRα and PPARγ was observed. Conclusions: Statins do not normalize pro-atherogenic changes induced by lupus and these changes continue to worsen over time. This study provides mechanistic insight into LAPS findings by demonstrating that statins are overall ineffective in altering the balance of cholesterol transport gene expression in human macrophages. Furthermore, our study suggests that statins as a CVD treatment may not be useful in attenuating lipid overload in the SLE environment.

scholarly journals Medicinal Plants and Atherosclerosis: A Review on Molecular Aspects

2018 ◽  
Vol 24 (26) ◽  
pp. 3123-3131 ◽  
Author(s):  
Sajedeh Gholipour ◽  
Robert D. E. Sewell ◽  
Zahra Lorigooini ◽  
Mahmoud Rafieian-Kopaei
Keyword(s):  
Medicinal Plants ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Inflammatory Factors ◽  
Atp Binding ◽  
Peroxisome Proliferator ◽  
Regulation Of Expression ◽  
Synthetic Drugs ◽  
Atp Binding Cassette Transporter ◽  
Atp Binding Cassette

Atherosclerosis is an inflammatory vascular disease that is characterized by progressive accumulation of cholesterol in the arterial walls and it is a major cause of cardiovascular disease. Issues related to the side effects of synthetic drugs have in recent times, led to the misuse of drugs, a lack of patient consultations, and consequently, a disruption in meticulous disease control. Therefore, a new insight into medicinal plants has recently emerged and much research has been conducted on these herbs in an attempt to prepare novel naturally based drugs. The aim of this review article was to scrutinize the molecular mechanisms of medicinal plants possessing effectiveness against atherosclerosis. To conduct the review, electronic searches were performed to retrieve potentially relevant publications, indexed within internet databases and reference textbooks concerning the effects and underlying molecular mechanisms of plants or their constituents used to treat atherosclerosis. Overall, medicinal plants facilitate atherosclerosis treatment through a variety of mechanisms which include the regulation of expression of inflammatory factors, stimulation of peroxisome proliferator-activated receptors (PPARs), inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), promotion of ATP-binding cassette transporter A1 (ABCA1) as well as ATP-binding cassette transporter G (ABCG), facilitation of adiponectin activity, reduction of sterol regulatory element-binding proteins (SREBPs) and antioxidant activity. An increased perception of these herbal mechanistic links is an important prelude to the design of novel plant based drugs.

scholarly journals Palmitoylation of ATP-Binding Cassette Transporter A1 Is Essential for Its Trafficking and Function

2009 ◽  
Vol 105 (2) ◽  
pp. 138-147 ◽  
Author(s):  
Roshni R. Singaraja ◽  
Martin H. Kang ◽  
Kuljeet Vaid ◽  
Shaun S. Sanders ◽  
Gonzalo L. Vilas ◽  
...  
Keyword(s):  
Atp Binding ◽  
Atp Binding Cassette Transporter ◽  
And Function ◽  
Atp Binding Cassette
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