Abstract
BackgroundAged garlic extract (AGE) and its main constituent S-allylcysteine (SAC) are natural antioxidants with protective effects against cerebral ischemia or cancer, events that involve hypoxia stress. Cobalt chloride (CoCl2) has been used to mimic hypoxic conditions through the stabilization of the α subunit of hypoxia inducible factor (HIF-1α) and up-regulation of HIF-1α-dependent genes as well as activation of hypoxic conditions such as reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential and apoptosis. The present study was designed to assess the effect of AGE and SAC on the CoCl2-chemical hypoxia model in PC12 cells.ResultsWe found that CoCl2 induced the stabilization of HIF-1α and its nuclear localization. CoCl2 produced ROS and apoptotic cell death that depended on hypoxia extent. The treatment with AGE and SAC decreased ROS and protected against CoCl2-induced apoptotic cell death which depended on the CoCl2 concentration and incubation time. SAC or AGE decreased the number of cells in the early and late stages of apoptosis. Interestingly, this protective effect was associated with attenuation in HIF-1α stabilization, activity not previously reported for AGE and SAC.ConclusionsObtained results show that AGE and SAC decreased apoptotic CoCl2-induced cell death. This protection occurs by affecting the activity of HIF-1α and supports the use of these natural compounds as a therapeutic alternative for hypoxic conditions.Electronic supplementary materialThe online version of this article (doi:10.1186/s40659-016-0067-6) contains supplementary material, which is available to authorized users.
Highlights
Aged garlic extract (AGE) and its main constituent S-allylcysteine (SAC) are natural antioxidants with protective effects against cerebral ischemia or cancer, events that involve hypoxia stress
Our results showed that the protective effect of SAC and AGE was due to the preservation of cell viability and a decrease in cell death, cobalt chloride (CoCl2)-induced apoptosis
The chemical hypoxia model induced by CoCl2 exposure in PC12 cells is a useful in vitro model to elucidate the mechanisms behind hypoxia damage and test novel compounds because it reproduces many hypoxic conditions, including reactive oxygen species (ROS) generation, mitochondrial membrane potential changes, induction of apoptosis [12,13,14,15,16] and HIF-1α-regulated transcriptional responses [8, 9]
Summary
Aged garlic extract (AGE) and its main constituent S-allylcysteine (SAC) are natural antioxidants with protective effects against cerebral ischemia or cancer, events that involve hypoxia stress. Cobalt chloride (CoCl2) has been used to mimic hypoxic conditions through the stabilization of the α subunit of hypoxia inducible factor (HIF-1α) and up-regulation of HIF-1α-dependent genes as well as activation of hypoxic conditions such as reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential and apoptosis. Hypoxic stress to cells alters gene expression regulation, leading to subsequent recovery processes or cell death. CoCl2 mimics several aspects of the hypoxic response, such as increasing and stabilizing HIF-1α protein through inhibition of Prolyl Hydroxylases (PHDs) activity and producing reactive oxygen species (ROS), which leads to cell damage, decreased cell viability and apoptosis [9,10,11]. Previous studies have clearly shown that CoCl2-induced cell damage is associated with an increase in ROS that subsequently induces apoptosis.
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