Protective effect of astaxanthin on the mitochondrial lesions induced by arsenic in HT-22 cells

CHEN Yao; YU Man; LIU Ying-jie; ZHANG Yi-xin; REN Hang; WANG Mei

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China Environmental Science ›› 2026, Vol. 46 ›› Issue (3) : 1646-1654.

Environmental Toxicology and Environmental Health

Protective effect of astaxanthin on the mitochondrial lesions induced by arsenic in HT-22 cells

CHEN Yao, YU Man, LIU Ying-jie, ZHANG Yi-xin, REN Hang, WANG Mei

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Abstract

This study focused on the protective mechanism of astaxanthin (AST) against arsenic-induced mitochondrial-dependent apoptosis in mouse hippocampal neuronal cells (HT-22). An in vitro sodium arsenite (NaAsO₂) exposure model was established in HT-22cells, including control, NaAsO₂-exposed (4, 6, 8, 10μmol/L), AST-treated (2μmol/L), and AST-intervened (2μmol/L AST + 10μmol/L NaAsO₂) groups, so as to evaluate the effects of AST intervention on arsenic-induced neural lesions. DCFH-DA was used to detect the level of reactive oxygen species (ROS). An ATP kit was used to assess the energy metabolism of mitochondria via ATP production. The levels of protein, including PGAM5 and signaling pathways of mitochondrial dynamics (fission/fusion), autophagy, and apoptosis, was analyzed by Western blot. Results showed that NaAsO₂ exposure significantly induced increased generation of ROS (P<0.05), decreased synthesis of ATP (P<0.05), activation of PGAM5, up-regulation of p-Drp1-Ser616, and down-regulation of p-Drp1-Ser637 and mitochondrial fusion proteins (OPA1, MFN1), leading to excessive mitochondrial fission. Intervention by AST effectively reversed these effects (P<0.05), which were demonstrated by the inhibition of PGAM5-mediated mitochondrial fission, alleviation of oxidative stress, and reversion of energy metabolism. It is supposed that AST plays a role in AMPK-mTOR-dependent autophagy and mitochondrial apoptosis. On one hand, AST inhibited AMPK phosphorylation which subsequently activated mTOR and down-regulated LC3II/LC3I ratio (autophagy marker); on the other hand, AST down-regulated pro-apoptotic proteins (Bax, cleaved-caspase-3), and upregulated anti-apoptotic Bcl-2 (P<0.05), thereby regulating AMPK-mTOR-dependent autophagy and mitochondrial apoptosis. This study suggests that AST protects against NaAsO₂-induced neurotoxicity by targeting PGAM5through the recovery of mitochondrial dynamics, improvement of energy metabolism, and regulation of AMPK-mTOR-autophagy-apoptosis axis, providing highlights on potential therapeutic strategies for arsenic-related neuronal damage.

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astaxanthin / arsenic / autophagy / apoptosis / neural damage

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CHEN Yao, YU Man, LIU Ying-jie, ZHANG Yi-xin, REN Hang, WANG Mei. Protective effect of astaxanthin on the mitochondrial lesions induced by arsenic in HT-22 cells[J]. China Environmental Science. 2026, 46(3): 1646-1654

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