Astaxanthine Secured Apoptotic Death of PC12 Cells Induced by β-Amyloid Peptide 25–35: Its Molecular Action Targets

Abstract

Astaxanthine (ASTx) is a novel carotenoid nutraceutical occurring in many crustaceans and red yeasts. It has potent antioxidant, photoprotective, hepatodetoxicant, and anti-inflammatory activities. Documented effect of ASTx on treatment of neurodegenerative disease is still lacking. We used the beta-amyloid peptide (Abeta) 25-35-treated PC12 model to investigate the neuron-protective effect of ASTx. The parameters examined included cell viability, caspase activation, and various apoptotic biomarkers that play their critical roles in the transduction pathways independently or synergistically. Results indicated that Abeta25-35 at 30 microM suppressed cell viability by 55%, whereas ASTx was totally nontoxic below a dose of 5.00 microM. ASTx at 0.1 microM protected PC12 cells from damaging effects of Abeta25-35 in several ways: (1) by securing the cell viability; (2) by partially down-regulating the activation of caspase 3; (3) by inhibiting the expression of Bax; (4) by completely eliminating the elevation of interleukin-1beta and tumor necrosis factor-alpha; (5) by inhibiting the nuclear translocation of nuclear factor kappaB; (6) by completely suppressing the phosphorylation of p38 mitogen-activated protein kinase; (7) by completely abolishing the calcium ion influx to effectively maintain calcium homeostasis; and (8) by suppressing the majority (about 75%) of reactive oxygen species production. Conclusively, ASTx may have merit to be used as a very potential neuron protectant and an anti-early-stage Alzheimer's disease adjuvant therapy.

Potential health‐promoting effects of astaxanthin: A high‐value carotenoid mostly from microalgae

“…Chang et al [101] recently found that astaxanthin showed an amazingly potent protective effect against the damaging effects elicited by b-amyloid peptide 25-35 in PC12 cells, and might be used as a very potential neuron protectant and a potent anti-Alzheimer's disease adjuvant therapy, particularly in its early stage.…”

Oleic acid ameliorates Aβ-induced inflammation by downregulation of COX-2 and iNOS via NFκB signaling pathway

“…Aβ residues are proteolytically produced by sequential action of β-secretase (BACE1) and γ-secretase from a single transmembrane amyloid precursor protein (APP). When secreted in low concentrations, Aβ not only protects the lipid from peroxidation but also plays a causal role in synapse and neuronal plasticity that underlies learning and memory (Chang, Chen, Chiou, Peng, & Peng, 2010). However, various experimental and genetic evidence demonstrated that abnormal extracellular deposition of Aβ is a pivotal and probably causal factor that initiates the neurotoxic cascade in AD (Whitehead, Hachinski, & Cechetto, 2005).…”

On the Neuroprotective Role of Astaxanthin: New Perspectives?

“…These cells were protected from neurotoxicity induced by 30 µM of beta-amyloid peptide, when treated with 0.1 µM of astaxanthin. This protective effect was due to caspase 3, Bax, IL-1β and TNFα, NF-κB inactivation, and suppression of ROS production [28]. Other studies have demonstrated the protective effect of astaxanthin on amyloid beta-induced generation of ROS and calcium dysregulation in primary hippocampal neurons [100] and the significant decrease of oxidative stress levels and cell death in PC12 cells injured with n-methyl-4-phenylpyridinium iodide (MPP+) [19].…”