Abstract
Background
Astrocytes do not only maintain homeostasis of the extracellular milieu of the neurons, but also play an active role in modulating synaptic transmission. Palmitic acid (PA) is a saturated fatty acid which, when being excessive, is a significant risk factor for lipotoxicity. Activation of astrocytes by PA has been shown to cause neuronal inflammation and demyelination. However, direct damage by PA to astrocytes is relatively unexplored. The aim of this study was to identify the mechanism(s) of PA-induced cytotoxicity in rat cortical astrocytes and possible protection by (+)-catechin.
Methods
Cytotoxicity and endoplasmic reticulum (ER) markers were assessed by MTT assay and Western blotting, respectively. Cytosolic Ca2+ and mitochondrial membrane potential (MMP) were measured microfluorimetrically using fura-2 and rhodamine 123, respectively. Intracellular reactive oxygen species (ROS) production was assayed by the indicator 2′-7′-dichlorodihydrofluorescein diacetate.
Results
Exposure of astrocytes to 100 μM PA for 24 h resulted in apoptotic cell death. Whilst PA-induced cell death appeared to be unrelated to ER stress and perturbation in cytosolic Ca2+ signaling, it was likely a result of ROS production and subsequent MMP collapse, since ascorbic acid (anti-oxidant, 100 μM) prevented PA-induced MMP collapse and cell death. Co-treatment of astrocytes with (+)-catechin (300 μM), an anti-oxidant found abundantly in green tea, significantly prevented PA-induced ROS production, MMP collapse and cell death.
Conclusion
Our results suggest that PA-induced cytotoxicity in astrocytes may involve ROS generation and MMP collapse, which can be prevented by (+)-catechin.
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Wong, KL., Wu, YR., Cheng, KS. et al. Palmitic acid-induced lipotoxicity and protection by (+)-catechin in rat cortical astrocytes. Pharmacol. Rep 66, 1106–1113 (2014). https://doi.org/10.1016/j.pharep.2014.07.009
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DOI: https://doi.org/10.1016/j.pharep.2014.07.009