Dicer-dependent cytoprotective effects of humanin against hypoxia-induced oxidative stress and mitochondrial dysfunction in microglial cells

Humanin appears to protect microglial cells from hypoxic injury, and Dicer is critical for this protective effect. Further research is needed to clarify the underlying mechanisms.

Summary and findings

This study investigated the role of Dicer in humanin-mediated cytoprotection against hypoxia-induced injury in BV2 microglial cells. Humanin improved cell viability and preserved mitochondrial function under hypoxic conditions. The reduction of Dicer expression attenuated the protective effects of humanin.

Abstract

<title>Abstract</title> <p>The mitochondria-derived peptide humanin is known for its potent cytoprotective properties. However, its functional association with the endoribonuclease Dicer under hypoxic stress remains unclear. This study investigated whether Dicer contributes to humanin-mediated cytoprotection against hypoxia-induced injury in microglial cells. BV2 microglial cells were exposed to CoCl₂-induced chemical hypoxia, and cell viability, intracellular and mitochondrial reactive oxygen species (ROS), and mitochondrial membrane potential were assessed. Stress-responsive and cell death-associated signaling pathways were examined by western blotting. To further examine the involvement of Dicer in humanin-mediated cytoprotection, Dicer expression was reduced using antisense oligonucleotides. Hypoxic stress reduced Dicer expression and induced microglial cell injury, accompanied by mitochondrial membrane depolarization, increased intracellular and mitochondrial ROS accumulation, activation of c-Jun N-terminal kinase (JNK) and p53 signaling, and induction of caspase-associated cell death signaling. Humanin significantly improved cell viability, attenuated oxidative stress, and preserved mitochondrial membrane potential under hypoxic conditions. Humanin also restored Dicer expression. Notably, reduction of Dicer substantially attenuated the protective effects of humanin on cell viability, oxidative stress, and stress- and cell death-associated signaling. These findings support a critical functional role for Dicer in humanin-mediated cytoprotection under hypoxic stress and identify a previously uncharacterized functional association between humanin and Dicer in microglial cells. Further studies are warranted to determine the molecular mechanisms underlying humanin-mediated regulation of Dicer and to establish whether downstream Dicer-dependent miRNA pathways contribute to this cytoprotective response.</p>

Limitations

Not reported in abstract.

Elsewhere in the Humanin corpus