α-Linolenic acid alleviates aluminium chloride-induced toxicity in PC12 ​cells by activation of PKA-CREB-BDNF signaling pathway

Abstract

Aluminum has been associated with neurodegenerative diseases. ALA (α-linolenic acid), an essential dietary component for human health, possesses prominent biological activities. Herein, we aim to explore the neuroprotective effects of ALA on aluminum toxicity and reveal the underlying mechanism. Results show that aluminum chloride (denoted as Al) enabled cell viability decline and apoptosis with oxidative stress and mitochondrial damage in differentiated rat pheochromocytoma cells (PC12) for 24 ​h incubation. Compared with Al (10 ​mmol/L) treatment alone, ALA (50 ​μmol/L) pretreatment for 24 ​h significantly enhanced cell viability by 28.40%, and hindered cell apoptosis by 12.35%, together with recovering redox state balance and alleviating mitochondrial damage. It was measured that ALA treatment upregulated Bcl-2 expression and down-regulated Bax level, accompanied with an expression decline of caspase-3 and caspase-9. Meanwhile, ALA pretreatment was proved to increase protein kinase A (PKA) expression and to promote phosphorylation of cAMP response element-binding protein (p-CREB), resulting in elevation on the level of brain-derived neurotrophic factor (BDNF). The above results showed that ALA attenuated Al toxicity in PC12 ​cells by mediating the PKA-CREB-BDNF signaling pathway.

Keywords

• Aluminium toxicity
• α-Linolenic acid
• PC12 ​cells
• Oxidative stress
• PKA-CREB-BDNF