Dexmedetomidine protects SH‐SY5Y cells against MPP⁺‐induced declining of mitochondrial membrane potential and cell cycle deficits

Abstract

Dexmedetomidine (Dex), an adrenergic α2 receptor agonist, is commonly used in deep-brain stimulation surgery for Parkinson's disease (PD). However, there is evidence that the use of anaesthetics may accelerate the progression of neurodegenerative diseases. The effect of Dex on PD remains unclear. Here, we cultured the all-trans-retinoicacid (ATRA) differentiated SH-SY5Y cells in vitro and then treated with MPP + (1.5mM) with or without Dex (10nM) or Dex combined with Atipamezole (Ati,100nM, adrenergic α2 receptor inhibitor). The ratio of apoptotic cells, mitochondrial membrane potential (Δψm), reactive oxygen species (ROS), cell cycle and apoptotic markers (Cleaved caspase-3, 9) were analysed by flow cytometry and immunofluorescence. We found that the levels of apoptotic ratio and cleaved caspase-3, 9 increased, ROS accumulated, and mitochondrial membrane potential decreased after MPP+treatment, while these changes were partially reversed by Dex.Dex also prevented MPP + induced cell arrest by increasing G1 phase cells, decreasing S phase cells, and decreasing the expression of cyclinD1 and Cdk4. Moreover the effects of Dex were partially reversed by Ati. These findings reveal that Dex attenuated MPP + -induced apoptosis of SH-SY5Y cells by preventing the loss of Δψm, reducing ROS, and regulating the cell cycle. Our findings indicated that Dex is more likely to be a potential drug for the treatment of PD.

A Novel Mitochondria-Targeting Iron Chelator Neuroprotects Multimodally via HIF-1 Modulation Against a Mitochondrial Toxin in a Dopaminergic Cell Model of Parkinson’s Disease

“…3), causing a high green/red ratio signal compared to the untreated control condition. This result is in line with several other studies that demonstrated the ability of MPP+ to accumulate inside mitochondria, followed by depolarization of the MMP [37][38][39]. This includes a recent study by Mapa and others [40], where the authors utilized experimental conditions that overlapped with the present work, namely a similar dosage of MPP+ (500μM), but with the cell line (undifferentiated MN9D cells) that differed from that used here.…”

Comparative proteomics study of mitochondrial electron transport system modulation in SH-SY5Y cells following MPP+ versus 6-OHDA-induced neurodegeneration

“…Finally, FACS experiments confirmed that mitochondrial dysfunction and apoptosis were increased in 6-OHDA-and MPP+-treated SH-SY5Y cells (Fig. 1E, F), as reported in previous studies (Wang et al 2014;Chen et al 2021;Ganapathy et al 2016). These results indicate that neurodegeneration was induced in 6-OHDA-and MPP+-treated SH-SY5Y cells that simulated PD.…”

Protopanaxadiols Eliminate Behavioral Impairments and Mitochondrial Dysfunction in Parkinson’s Disease Mice Model

“…Existing studies have shown that the increase of ROS and the decrease of ATP caused by mitochondrial dysfunction promote oxidative stress response, aging and neurodegenerative changes, which promote the occurrence and development of PD [ 54 , 55 ]. MPP + inhibits the function of respiratory complex I, interferes with the mitochondrial electron transport chain, and eventually leads to the decrease of mitochondrial membrane potential, the increase of ROS, and mitochondrial damage [ 55 , 56 ]. We observed that PPDs treatment restored mitochondrial membrane potential and reduced ROS accumulation, suggesting that PPDs could rescue mitochondrial dysfunction.…”