Effects of <i>Salidroside</i> on Cobalt Chloride-Induced Hypoxia Damage and mTOR Signaling Repression in PC12 Cells

Abstract

Salidroside (SA), a phenylpropanoid glycoside isolated from Rhodiola rosea L., has been documented to exert a broad spectrum of pharmacological properties, including protective effects against neuronal death induced by various stresses. To provide further insights into the neuroprotective functions of SA, this study examined whether SA can attenuate cobalt chloride (CoCl 2 )-induced hypoxia damage and mammalian target of rapamycin (mTOR) signaling repression in PC12 differentiated cells. Differentiated PC12 cells were exposed to CoCl 2 for 12 h to mimic hypoxic/ischemic conditions and treated with SA at the same time, followed by electron microscopy and analysis of cell viability, intracellular reactive oxygen species ( Key words salidroside; ischemic; mammalian target of rapamycin (mTOR); hypoxia; cobalt chloride; PC12 cell Focal cerebral ischemia or stroke is characterized by obstruction of blood flow to the brain, resulting in deficient supply of oxygen, glucose, serum, and nutrient that are indispensable for the energy generation. Since central nervous system is most susceptible to hypoxia conditions, the continuous oxygen and energy deprivation results in cognitive disturbances and decreased motor control, leading to fainting, long term loss of consciousness, coma, seizures, cessation of brain stem reflexes, and brain death. Ischemic stroke is currently a leading cause of disability and mortality in the aged population, due to limited medication and therapy, and new therapeutic strategies for this devastating disease are urgently needed.Recently, the role of mammalian target of rapamycin (mTOR) signaling in neurodegenerative and cerebrovascular diseases has attracted great attention.

The neurotoxicity of iron, copper and cobalt in Parkinson’s disease through ROS-mediated mechanisms

“…More recently, it has been reported that CoCl 2 -mediated repression of mechanistic target of rapamycin (mTOR) signaling could be significantly alleviated by an antioxidant in PC12 cells, which suggests that CoCl 2 suppresses mTOR signaling via ROS (Zhong et al 2014). Aside from mTOR signaling, endothelin system which is important for vascular homeostasis could also be modulated by CoCl 2 .…”

“…The inflammatory response in PC12 cells upon CoCl 2 treatment could be blocked by NAC, suggesting that CoCl 2 -induced inflammatory response correlates with oxidative stress in PC12 cells (Zhong et al 2014;Kotake-Nara et al 2005;Kotake-Nara and Saida 2006;Lan et al 2013). It is well known that astrocytes, as the major glial population, play an important role in the central nervous system (CNS).…”

Rhodiola rosea L.: from golden root to green cell factories

“…In addition to its protective effects against oxidative stress, salidroside also protects against hypoxia-mediated damage in cultured cardiomyocytes and PC12 cells Zhong et al 2014), and in vivo in mice (Huang et al 2015). The latter study examined the effect of salidroside in a mouse model of pulmonary arterial hypertension induced by chronic hypoxia.…”

Insights into the therapeutic potential of hypoxia-inducible factor-1&alpha; small interfering RNA in malignant melanoma delivered via folate-decorated cationic liposomes

“…Afterward, the chemical anoxic agent CoCl 2 was added to the cells to achieve a hypoxic induction with a concentration of 100 μM. 24 The hypoxia-induced cells were subcultured in multi-well plates and subsequently used for various cell experiments.…”