Carboxylic Acid Fullerene (C60) Derivatives Attenuated Neuroinflammatory Responses by Modulating Mitochondrial Dynamics

Abstract

Fullerene (C60) derivatives, a unique class of compounds with potent antioxidant properties, have been reported to exert a wide variety of biological activities including neuroprotective properties. Mitochondrial dynamics are an important constituent of cellular quality control and function, and an imbalance of the dynamics eventually leads to mitochondria disruption and cell dysfunctions. This study aimed to assess the effects of carboxylic acid C60 derivatives (C60–COOH) on mitochondrial dynamics and elucidate its associated mechanisms in lipopolysaccharide (LPS)-stimulated BV-2 microglial cell model. Using a cell-based functional screening system labeled with DsRed2-mito in BV-2 cells, we showed that LPS stimulation led to excessive mitochondrial fission, increased mitochondrial localization of dynamin-related protein 1 (Drp1), both of which were markedly suppressed by C60–COOH pretreatment. LPS-induced mitochondria reactive oxygen species (ROS) generation and collapse of mitochondrial membrane potential (ΔΨm) were also significantly inhibited by C60–COOH. Moreover, we also found that C60–COOH pretreatment resulted in the attenuation of LPS-mediated activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling, as well as the production of pro-inflammatory mediators. Taken together, these findings demonstrated that carboxylic acid C60 derivatives may exert neuroprotective effects through regulating mitochondrial dynamics and functions in microglial cells, thus providing novel insights into the mechanisms of the neuroprotective properties of carboxylic acid C60 derivatives.

C60 Fullerene Reduces 3-Nitropropionic Acid-Induced Oxidative Stress Disorders and Mitochondrial Dysfunction in Rats by Modulation of p53, Bcl-2 and Nrf2 Targeted Proteins

“…Numerous C 60 positive effects were determined mainly by the antioxidant capacity of C 60 , which was several hundred times higher than that of other antioxidants [ 21 , 22 , 23 , 24 , 25 ]. Recently, water-soluble fullerenes attracted great attention in neurosciences [ 26 , 27 , 28 ]. The brain contains many different unsaturated fatty acids, and it also has limited ability to regenerate damaged tissues.…”

Drp1-Dependent Mitochondrial Fission Mediates Toxicity of Positively Charged Graphene in Microglia

“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 8 pDsRed2-Mito (Clontech, Palo Alto, CA, USA) after reaching 70-80% confluence as described. 27 This vector encodes red fluorescent protein derived from Dicosoma sp.…”

C60 Fullerenes Suppress Reactive Oxygen Species Toxicity Damage in Boar Sperm

“…Hence, the obtained data sufficiently expand our knowledge concerning the potential involvement of fullerene nanostructures in processes that occur in sperm at 4 °C in vitro. Indeed, based on their antioxidant properties, fullerenes have been shown to have protective effects in various cell types [41][42][43] and within multifarious disease contexts [44][45][46][47]. It is worth mentioning that carboxylated C 60 has recently been demonstrated to be able to inactivate free radicals (ROS) with values that substantially exceed the theoretically expected level.…”