Astaxanthin effect on tissue transglutaminase expression in human neuronal differentiated stem cells exposed to hypoxia and hypoxia/reoxygenation

Astaxanthin represents a natural antioxidant compound extracted from marine organisms, showing neuroprotective effects. In this study, for the first time, we highlighted the effect of astaxanthin pre-treatment on localization and expression of tissue transglutaminase isoforms (TG2-L and TG2-S) in human Neuronal Cells Differentiated from Human Dental Pulp Stem Cells (hNCs) exposed to hypoxia and/or hypoxia/reoxygenation. The percentage of cell viability, mitochondrial membrane potential and caspase-3 cleavage were evaluated. In particular, TG2 is involved in hypoxia diseases, playing different roles on the basis of its localization and conformation state. Our results highlight a significant increase of isoforms levels in hypoxia and/or hypoxia/reoxygenation, compared with the normoxia condition. In hypoxia and/or hypoxia/reoxygenation a significant decrease of the percentage of cell viability, an alteration mitochondrial membrane potential and the activation of the apoptotic pathway were observed. Astaxanthin pre-treatment was able to counteract the excitotoxic effect induced by hypoxia and/or hypoxia/reoxygenation, restoring TG2 isoform levels, the percentage of cell viability and the mitochondrial membrane potential to normoxia condition, inhibiting also apoptotic pathway activation. Our data highlight that astaxanthin could represent a candidate adjuvant for neural regeneration under hypoxic conditions, acting on the TG2 state, which plays a key role in apoptosis and self-renewal capacity.