Macrophage mitochondrial damage from StAR transport of 7-hydroperoxycholesterol: implications for oxidative stress-impaired reverse cholesterol transport. FEBS Lett 2014 Jan 03;588(1):65-70
Date
11/26/2013Pubmed ID
24269887DOI
10.1016/j.febslet.2013.10.051Scopus ID
2-s2.0-84890988812 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
StAR family proteins in vascular macrophages participate in reverse cholesterol transport (RCT). We hypothesize that under pathophysiological oxidative stress, StARs will transport not only cholesterol to macrophage mitochondria, but also pro-oxidant cholesterol hydroperoxides (7-OOHs), thereby impairing early-stage RCT. Upon stimulation with dibutyryl-cAMP, RAW264.7 macrophages exhibited a strong time-dependent induction of mitochondrial StarD1 and plasma membrane ABCA1, which exports cholesterol. 7α-OOH uptake by stimulated RAW cell mitochondria (like cholesterol uptake) was strongly reduced by StarD1 knockdown, consistent with StarD1 involvement. Upon uptake by mitochondria, 7α-OOH (but not redox-inactive 7α-OH) triggered lipid peroxidation and membrane depolarization while reducing ABCA1 upregulation. These findings provide strong initial support for our hypothesis.
Author List
Korytowski W, Wawak K, Pabisz P, Schmitt JC, Girotti AWMESH terms used to index this publication - Major topics in bold
ATP Binding Cassette Transporter 1Animals
Biological Transport
Blotting, Western
Bucladesine
Cell Line
Cell Membrane
Cell Survival
Cholesterol
Dose-Response Relationship, Drug
Lipid Peroxidation
Macrophages
Membrane Potential, Mitochondrial
Mice
Mitochondria
Oxidative Stress
Phosphoproteins
RNA Interference
Time Factors
