Back to Search
Start Over
Modulatory role of HMG-CoA reductase inhibitors and ezetimibe on LDL-AGEs-induced ROS generation and RAGE-associated signalling in HEK-293 Cells.
- Source :
-
Life Sciences . Oct2019, Vol. 235, pN.PAG-N.PAG. 1p. - Publication Year :
- 2019
-
Abstract
- Advanced glycation end products (AGEs) trigger intracellular reactive oxygen species (ROS) generation, activation of receptor for AGEs (RAGE) expression/functionality and RAGE-associated signalling pathways which influence the diabetic-cum-atherosclerotic complications, whereas, the atherosclerosis progression is greatly influenced by hepatic β-Hydroxy-β-methyl-glutaryl-Co-A reductase (HMG-R) activity. The present report was premeditated to uncover the regulatory role of HMG-R inhibitors and ezetimibe (EZ) in attenuating the LDL-AGEs-induced pathogenicity via targeting cellular-ROS and RAGE-associated signalling in HEK-293 cells. The MTT assay was used to assess either the cytotoxic or cytoprotective impact of each HMG-R inhibitors, EZ, and LDL-AGEs, whereas, quantification of ROS was performed by DCFDA method. The qRT-PCR was used to detect the mRNA level of RAGE, neuropilin-1 (NRP-1) and other RAGE-associated genes like MMP-2, NF-κB, and TGFβ-1. The HMG-R inhibitors do not exert any cytotoxicity in HEK-293 cells, whereas, and LDL-AGEs negatively affected the cell viability of HEK-293 cells. However, viability of LDL-AGEs-treated HEK-293was markedly retained after simultaneous treatment with our test inhibitors. Further, DCFDA staining showed that LDL-AGEs-induced ROS was also suppressed upon treatment with our test inhibitors in HEK-293 cells. qRT-PCR analysis reflected that these inhibitors suppress the RAGE, NF-κB, TGFβ-1, and MMP-2 expression, whereas, the NRP-1 was up-regulated by these compounds in LDL-AGEs-exposed HEK-293 cells. The above pharmacological effects signify that HMG-R inhibitors and EZ (alone or in combination) may implied in the treatment of AGEs-induced oxidative stress and tissue damage in diabetic complications via targeting intracellular-ROS, NRP-1 functionality and RAGE-associated genes i.e. NF-κB, TGFβ-1, and MMP-2. Unlabelled Image [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00243205
- Volume :
- 235
- Database :
- Academic Search Index
- Journal :
- Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 139239033
- Full Text :
- https://doi.org/10.1016/j.lfs.2019.116823