Melatonin Treatment Regulates SIRT3 Expression in Early Brain Injury (EBI) Due to Reactive Oxygen Species (ROS) in a Mouse Model of Subarachnoid Hemorrhage (SAH)
Song Yang, Xiuping Chen, Shengli Li, Bin Sun, Chunhua Hang
Department of Neurosurgery, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, China (mainland)
Med Sci Monit 2018; 24: LBR3804-3814
Available online: 2018-06-06
A mouse model of subarachnoid hemorrhage (SAH) investigated the effects of melatonin treatment on the generation of reactive oxygen species (ROS) and the activation of the SIRT3 gene in early brain injury (EBI).
MATERIAL AND METHODS: Male C57BL/6J mice were assigned to three groups: the SAH group; the sham group; and the SAH + melatonin-treated group (intraperitoneal dose, 150 mg/kg). TUNEL was used to study apoptosis of neuronal cells, Western-blot and immunohistochemistry detected expression of Sirt3, Bcl-2, superoxide dismutase 2 (SOD2), Bax, and cleaved caspase-3. Real-time polymerase chain reaction (PCR) and a luciferase reporter assay evaluated the effects of melatonin on SIRT3 gene expression. Malondialdehyde (MDA) and the reactive oxygen species (ROS) scavenger, reduced glutathione (GSH), and its ratio with oxidized glutathione (GSSG) was measured.
RESULTS: The increase in neurological score and increase in cerebral edema following SAH were reduced in the SAH + melatonin-treated group. Neuronal apoptosis following SAH was reduced in the SAH + melatonin-treated group. Increased levels of SOD2, Bax, and cleaved caspase-3 following SAH were reduced in the SAH + melatonin-treated group; reduced levels of Sirt3 and Bcl-2 following SAH were increased in the SAH + melatonin-treated group. The GSH: GSSG ratio was increased, and the MDA level was decreased when melatonin treatment was used following SAH. Melatonin upregulated SIRT3 expression by increasing the transcription efficiency of the SIRT3 promoter in human glioma cell lines U87 and U251.
CONCLUSIONS: Melatonin provided protection from the effects of EBI following SAH by regulating the expression of murine SIRT3.
Keywords: Brain Injuries, Melatonin, Sirtuin 3, Subarachnoid Hemorrhage