10 research outputs found
GD2 ganglioside-binding antibody 14G2a and specific aurora A kinase inhibitor MK-5108 induce autophagy in IMR-32 neuroblastoma cells
The role of sterol transport proteins from the StAR family in promoting oxidative stress by cholesterol hydroparoxides 7-OOH in activated macrophage cells : mechanism and cytotoxic consequences
Zaburzenia homeostazy transportu cholesterolu s膮 sercem powsta艂ych zmian mia偶d偶ycowych. W ich trakcie kom贸rki makrofag贸w zostaj膮 prze艂adowane cholesterolem i innymi lipidami, podczas wch艂aniania utlenionych lipoprotein o niskiej g臋sto艣ci (oxLDL). W sk艂ad oxLDL wchodz膮 r贸偶ne formy utlenionego cholesterolu (np. 7=O, 7-OH, 7-OOH), ale tylko wodoronadtlenki cholesterolu ChOOH, takie jak 7-OOH, s膮 oksydoredukcyjnie aktywne. Aby ograniczy膰 szkodliw膮 akumulacj臋 cholesterolu, makrofagi posiadaj膮 mechanizm jego eksportu do akceptor贸w zewn膮trzkom贸rkowych, takich jak apolipoproteina A-I (apoA-I) lub lipoproteina o du偶ej g臋sto艣ci (HDL). Jest to wczesny etap zwrotnego transportu cholesterolu (RCT), w kt贸rym cholesterol dostarczany jest do w膮troby w celu jego usuni臋cia. Proces RCT jest niezb臋dny w utrzymaniu homeostazy cholesterolu. Makrofagi posiadaj膮 wiele bia艂ek, kt贸re bior膮 udzia艂 w RCT. Obejmuj膮 one bia艂ka bia艂ka z grupy ostrych regulator贸w steroidogenezy (StAR), kt贸re wi膮偶膮 i transportuj膮 cholesterol, dostarczaj膮c go do mitochondri贸w. W pracy tej wykazano, 偶e w warunkach stresu oksydacyjnego, bia艂ka StAR mog膮 przenosi膰 do mitochondri贸w makrofag贸w nie tylko cholesterol, ale tak偶e 7-OOH, prowadz膮c do zaburzenia wczesnych etap贸w RCT. Po dostarczeniu do mitochondrium, 7-OOH inicjowa艂o peroksydacj臋 lipid贸w i depolaryzacj臋 b艂ony mitochondrialnej. Dostarczenie 7-OOH do mitochondri贸w makrofag贸w spowodowa艂o r贸wnie偶 zmniejszenie ekspresji STARD1, redukcj臋 produkcji 27-OH oraz zmniejszenie ekspresji bia艂ka ABCA1. Zmiany te doprowadzi艂y do zmniejszenia eksportu cholesterolu do apoA-I i HDL. Praca ta dostarcza zatem nowych informacji o mo偶liwej roli peroksydacji lipid贸w, dysfunkcji makrofag贸w oraz patogenezie mia偶d偶ycy. Jest to nowy mechanizm, 艣ci艣le powi膮zany ze schorzeniami skorelowanymi ze stresem oksydacyjnym.Disorders of the macrophage cholesterol transport homeostasis are the heart of formed atherosclerotic lesions. During this process, macrophages may potentially be overloaded with cholesterol and other lipids when oxidized Low Density Lipoprotein (oxLDL) is taken up. OxLDL contains varies of oxidized cholesterol forms (e.g. 7=O, 7-OH, 7-OOH), but only hydroperoxycholesterols ChOOH, such as 7-OOHs, are redox-active. To limit the harmful cholesterol accumulation, macrophages have mechanisms to export it to extracellular acceptors such as apolipoprotein A-I (apoA-I) or High Density Lipoprotein (HDL). This is an early step of reverse cholesterol transport (RCT), which delivers cholesterol to the liver for disposal. RCT is an essential in the maintenance of cholesterol homeostasis. Macrophages express a number of proteins, which participate in RCT. These include steroidogenic acute regulatory family proteins (StAR) which bind and transport cholesterol, delivering it to the mitochondria. This study demonstrates that under oxidative stress, StARs can transport not only cholesterol to macrophage mitochondria but also 7-OOH, thereby impairing early-stage RCT. Upon uptake by mitochondrion, 7-OOH initiated lipid peroxidation and membrane depolarization. Moreover, the administration of 7-OOH to cells decreased expression of STARD1 and resulted in a decrease in production of 27-OH and a reduction in ABCA1 expression, and thus reduced the release of cholesterol to apoA-I and HDL. Therefore, this study provides new information about the possible role of lipid peroxidation, macrophage dysfunction and the pathogenesis of atherosclerosis. This is a new mechanism, closely related to diseases correlated with oxidative stress
Enhanced aggressiveness of bystander cells in an anti-tumor photodynamic therapy model : role of nitric oxide produced by targeted cells
Macrophage mitochondrial damage from StAR transport of 7-hydroperoxycholesterol : implications for oxidative stress-impaired reverse cholesterol transport
AbstractStAR 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. 7伪-OOH uptake by stimulated RAW cell mitochondria (like cholesterol uptake) was strongly reduced by StarD1 knockdown, consistent with StarD1 involvement. Upon uptake by mitochondria, 7伪-OOH (but not redox-inactive 7伪-OH) triggered lipid peroxidation and membrane depolarization while reducing ABCA1 upregulation. These findings provide strong initial support for our hypothesis
Impairment of macrophage cholesterol efflux by cholesterol hydroperoxide trafficking : implications for atherogenesis under oxidative stress
Macrophage mitochondrial damage from StAR transport of 7-hydroperoxycholesterol: Implications for oxidative stress-impaired reverse cholesterol transport
Pa艅stwo demokratyczne, prawne i socjalne: ksi臋ga jubileuszowa dedykowana profesorowi Zbigniewowi Antoniemu Maci膮gowi. T. 3, Studia prawne
Praca recenzowana / peer-reviewed pape