Rat ATP Binding Cassette Transporter A1 ELISA Kit

Background and Purpose.Alterations in cholesterol homeostasis have been reported in cell and animal models of Parkinson's disease (PD), although there are inconsistent data about the association between serum cholesterol levels and risk of PD. Here, we investigated the effects of miR-873 on lysosomal cholesterol homeostasis and progressive dopaminergic neuron damage in a lipopolysaccharide-(LPS) induced model of PD.Experimental Approach. To evaluate the therapeutic benefit of the miR-873 sponge, rats were injected with a LV-miR-873 sponge or the control vector 3 days before the right-unilateral injection of LPS into the substantia nigra (SN) pars compacta, or 8 and 16 days after LPS injection. Normal SH-SY5Y cells or SH-SY5Y cells overexpressing alpha-synuclein were used to evaluate the distribution of alpha-synuclein and cholesterol in lysosomes and to assess the autophagic flux after miR-873 transfection or ABCA1 silencing. The inhibition of miR-873 significantly ameliorated the LPS-induced accumulation of alpha-synuclein and loss of dopaminergic neurons in the SN at the early stage. miR-873 mediated the inhibition of ABCA1 by LPS. miR-873 transfection or ABCA1 silencing increased the lysosomal cholesterol and alpha-synuclein levels, and decreased the autophagic flux. The knockdown of ABCA1 or A20, which are the downstream target genes of miR-873, exacerbated the damage to LPS-induced dopaminergic neurons.Conclusion and Implications. The results suggest that the inhibition of miR-873 may play a dual protective role by improving intracellular cholesterol homeostasis and neuroinflammation in PD. The therapeutic effects of the miR-873 sponge in PD may be due to the upregulation of ABCA1 and A20.

Atherosclerosis (AS), a major cause of cardiovascular disease, has developed into a serious challenge to the health system. The long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is associated with the pathogenesis of AS. However, whether MALAT1 can affect cholesterol accumulation in macrophages during AS progression, and the potential molecular mechanism involved in this progression have not been elucidated. In the present study, the mRNA expression level of MALAT1 was measured using reverse transcription-quantitative PCR (RT-qPCR) and the protein expression level was detected via western blot analysis. Oil Red O staining was used for detecting lipid accumulation in macrophages. Bioinformatics, dual-luciferase reporter and RT-qPCR assays were used to investigate the relationship between MALAT1 and the microRNA (miR)-17-5p/ATP-binding cassette transporter A1 (ABCA1) axis. The present results suggested that the MALAT1 expression level was significantly decreased in patients with AS and in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages. Knockdown of MALAT1 increased ox-LDL uptake, lipid accumulation and the total cholesterol (T-CHO) level in ox-LDL-induced macrophages. In addition, MALAT1 inhibition significantly decreased the mRNA and protein expression levels of scavenger receptor (SR) class B member 1, apolipoprotein E (ApoE) and ABCA1. However, MALAT1 increased the expression level of SR class A. Subsequently, the present study investigated whether MALAT1 could target miR-17-5p to regulate the expression level of ABCA1, which is involved in cholesterol efflux from macrophages. The present results suggested that inhibition of miR-17-5p reversed the effects of MALAT1 knockdown on T-CHO content, and protein expression levels of ApoE and ABCA1 in ox-LDL-stimulated macrophages. In summary, knockdown of MALAT1 may promote cholesterol accumulation by regulating the miR-17-5p/ABCA1 axis in ox-LDL-induced THP-1 macrophages.