Effects and mechanism of lipoic acid on beta-amyloid-intoxicated C6 glioma cells

Abstract

ABSTRACT. β-amyloid peptides (Aβs) can exert neurotoxic effects through induction of oxidative damage, whereas lipoic acid (LA), a powerful antioxidant, can alleviate oxidative damage. In this study, we explored the effect and mechanism of action of LA on beta-amyloidintoxicated C6 glioma cells. Cells were randomly divided into three groups: control (vehicle), Aβ, and LA + Aβ. The LA + Aβ group was treated with LA for 2 h, then both the Aβ-only and the LA + Aβ groups were incubated with 25 μM Aβ for 24 h. Cell viability was measured by the MTT method. Mitochondrial reduced glutathione (GSH) and oxidized glutathione (GSSG) levels were detected by enzyme-linked immunosorbent assay (ELISA), and the GSH to GSSG ratio calculated. Real-time polymerase chain reaction and western blot analyses were used to detect MnSOD mRNA and protein, respectively. Aβ significantly inhibited C6 cell proliferation compared with the control group (P < 0.05). LA markedly increased cell viability compared with the Aβ group (P < 0.05). The increased GSSH and decreased GSH mitochondrial accumulation induced by Aβ was profoundly reversed by treatment with LA (P < 0.05). Aβ significantly reduced MnSOD expression compared to controls (P < 0.05), whereas LA pretreatment increased MnSOD expression compared with the Aβ-only group (P < 0.05); MnSOD protein levels showed similar patterns. These results suggest that LA might protect Aβ-intoxicated C6 glioma cells by alleviating oxidative damage, providing a new treatment strategy for neurodegenerative diseases.

Biochemical and clinical relevance of alpha lipoic acid: antioxidant and anti-inflammatory activity, molecular pathways and therapeutic potential

“…These research findings demonstrate the practicability of supplementation of lipoic acid to improve the treatment of AD symptoms. Another interesting study [83] demonstrated that Ab peptides could significantly inhibit the proliferation of C6 cells, while LA could reverse the inhibition effect of Ab and promote the recovery of cell viability. Ab exposure was also found to decrease the ratio of GSH and GSSH, and it reduced the expression of both MnSOD mRNA and protein in the mitochondria of C6 cells.…”

Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration

“…LA may be obtained from the diet (Packer et al, 1997 ; Hagen et al, 1999 ; Morikawa et al, 2001 ; Ghibu et al, 2009 ) and due to its capability of endogenous synthesis it is not considered a vitamin (Packer et al, 1995 , 2001 ; Bast and Haenen, 2003 ), but is structurally considered a member of the vitamin B family (Xing et al, 2015 ). When ingested as a nutritional supplement preferably in the racemic mixture form, LA contains two isomers (1:1 of R-LA and S-LA), in which S-LA may prevent polymerization of R-LA and thus increases the bioavailability of the later (De Araujo et al, 2011 ).…”

“…There are many studies examining the neuroprotective actions of LA using in vitro models of neurodegeneration (Tirosh et al, 1999 ; Li et al, 2013 ; Xing et al, 2015 ), most of which focus on AD. For example, Ono et al ( 2006 ) investigated the effects of LA and its reduced form, DHLA, on the formation, extension, and destabilization of β-amyloid fibrils (fAβ).…”

“…In β-amyloid-intoxicated C6 glioma cells, LA increased cell viability and MnSOD expression. The increased GSSH and decreased GSH mitochondrial levels induced by Aβ were reversed by treatment with LA (Xing et al, 2015 ). In addition, LA protected cortical neurons against Aβ peptide- and hydrogen peroxide-induced damage, suggesting that the neuroprotective effects were partly related to PKB/Akt signaling pathway stimulation (Zhang et al, 2001 ).…”

Hydroxytyrosol restores proper insulin signaling in an astrocytic model of Alzheimer's disease

“…The (25-35) fragment of Ab is widely used in cellular cultures to approximate the astrocytic damage induced by Ab in the brain of AD patients, because several studies have demonstrated that Ab is able to pass the cell membrane and exerts cytotoxic effects both on astrocytes and neurons [9,50]. Several authors used our astrocytic "in vitro" model of AD (astrocytes treated with Ab) to assess the effects of different molecules on diverse Ab-induced damages in astrocytes, for example [51,52]. Moreover, intracerebroventricular injections of Ab(25-35) cause learning and memory impairments similar to those of AD, in mice [53].…”