Lipid Droplets: Their Role in Nanoparticle-Induced Oxidative Stress

Abstract

Lipid droplets are cytoplasmic organelles found in almost all cells under physiological or pathological conditions. Certain nanoparticles can induce lipid droplet formation under oxidative stress conditions. Small metallic nanoparticles such as cadmium telluride (CdTe) nanoparticles, particularly those with incompletely protected surfaces, induce oxidative stress and may inflict damages to several intracellular organelles. The objective of this study was to assess formation of lipid droplets in cells treated with CdTe nanoparticles and relate their status to cell function (mitochondrial activity and cell viability). Multicolor labeling of cellular organelles (lipid droplets and lysosomes) showed that lipid droplets formed in pheochromocytoma (PC12) cells following nanoparticle or oleic acid treatment. Some lipid droplets were found closely apposed to lysosomes suggesting possible communication between these organelles during severe oxidative stress. Combination of microscopy of living cells with cell viability assays showed that oleic acid-induced lipid droplets not only serve as intracellular lipid storage sites but also play a protective role in starving stressed cells. Results from these studies suggest that oleic acid-induced LD in PC12 cells are dynamic and adaptive organelles, which provide energy to starving cells and facilitate their rescue under starvation and exposure to metallic nanoparticles.

Differential stress reaction of human colon cells to oleic-acid-stabilized and unstabilized ultrasmall iron oxide nanoparticles

“…Thus, even if OA-USPIO NPs were poorly taken up by the cells, the oleic acid coating of USPIO NPs changed the cell response to the otherwise nontoxic NS-USPIO NPs. LDs are cytoplasmic dynamic organelles and are found in most cells, 33 either under normal or pathological conditions. Their number and size varies under cell stress conditions.…”

“…Exposure of murine glial cells to cadmium-telluride (CdTe) or InGaP/ZnS NPs, but also to oleic acid, induced the formation of LDs, some of them located close to lysosomes, possibly playing a protective function in stressed cells and a rescue role for cells exposed to CdTe NPs or controlling the cellular distribution of the InGaP/ZnS NPs. 33,35 Oleic-acid-induced lipid accumulation was shown in smooth muscle cells, which became foam cells, a mechanism not limited to macrophages. 36 It was shown in human hepatoma cells that both oleic-acid-stabilized and unstabilized USPIO NPs induced cell arrest in the G1 phase, but OA-USPIO NPs induced less cell damage than unstabilized USPIO NPs.…”

Mechanisms of cellular adaptation to quantum dots – the role of glutathione and transcription factor EB

“…Exposure to both artificial and biological NPs can lead to the disruption of cellular redox status and activation of compensatory mechanisms. However, when exposed to toxic nanomaterials for a short time or in low nanomolar concentrations, cells can successfully adapt by engaging antioxidant defenses and lipid re-distribution processes (Jain et al 2009;Khatchadourian and Maysinger 2009). Specific mechanisms that mediate these adaptive cellular processes remain unclear.…”

“…Indeed, activation of Nrf2 in response to GSH depletion is an important determinant of cellular fate (Li et al 2007). Dynamic changes in the lysosomal compartment following oxidative stress are also believed to play a role in the cellular adaptation process (Khatchadourian and Maysinger 2009). …”

“…The protein product of one of these genes, lysosomal-associated membrane protein 1 (LAMP1), plays a key role in lysosome biogenesis, stability and function (Eskelinen 2006). Recent studies have shown that most QDs tend to accumulate in lysosomal compartments and may themselves induce lysosome formation Khatchadourian and Maysinger 2009;Przybytkowski et al 2009). Our hypothesis is that activation of TFEB drives many of the observed changes in the cellular lysosomal compartment in response to QDinduced oxidative stress.…”