title: Aged garlic extract and S-allylcysteine prevent apoptotic cell death in a chemical hypoxia model.
abstract: BACKGROUND
  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. The present study was designed to assess the effect of AGE and SAC on the CoCl2-chemical hypoxia model in PC12 cells.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Obtained 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.
authors.affiliation: Laboratorio de Neurobiología Molecular y Celular, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Delegación Tlalpan, 14269, Mexico, D.F., Mexico. marisol.orozco.ibarra@gmail.com.
authors.forename: Marisol
authors.initials: M
authors.lastname: Orozco-Ibarra
authors.affiliation: Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Av. Insurgentes Sur # 3877, Colonia La Fama, Delegación Tlalpan, 14269, Mexico D.F., Mexico. jorgemen89@hotmail.com.
authors.forename: Jorge
authors.initials: J
authors.lastname: Muñoz-Sánchez
authors.affiliation: Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Av. Insurgentes Sur # 3877, Colonia La Fama, Delegación Tlalpan, 14269, Mexico D.F., Mexico. anneniv@gmail.com.
authors.forename: Martín E
authors.initials: ME
authors.lastname: Zavala-Medina
authors.affiliation: Laboratorio de Neuroinmunología y Neuro-oncología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Delegación Tlalpan, 14269, Mexico D.F., Mexico. benpio76@hotmail.com.
authors.forename: Benjamín
authors.initials: B
authors.lastname: Pineda
authors.affiliation: Laboratorio de Neuroinmunología y Neuro-oncología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Delegación Tlalpan, 14269, Mexico D.F., Mexico. roxytbp@yahoo.com.mx.
authors.forename: Roxana
authors.initials: R
authors.lastname: Magaña-Maldonado
authors.affiliation: Departamento de Ciencias Naturales, CNI, Universidad Autónoma Metropolitana Cuajimalpa, Av. Vasco de Quiroga 4871: Col. Santa Fe, Delegación Cuajimalpa de Morelos, 05348, Mexico D.F., Mexico. evazquezc@gmail.com.
authors.forename: Edgar
authors.initials: E
authors.lastname: Vázquez-Contreras
authors.affiliation: Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Av. Insurgentes Sur # 3877, Colonia La Fama, Delegación Tlalpan, 14269, Mexico D.F., Mexico. maldonado.perla@gmail.com.
authors.forename: Perla D
authors.initials: PD
authors.lastname: Maldonado
authors.affiliation: Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510, Mexico D.F., Mexico. pedraza@unam.mx.
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
authors.affiliation: Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Av. Insurgentes Sur # 3877, Colonia La Fama, Delegación Tlalpan, 14269, Mexico D.F., Mexico. echanezc@gmail.com.
authors.forename: María Elena
authors.initials: ME
authors.lastname: Chánez-Cárdenas
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051792:Basic Helix-Loop-Helix Proteins / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003035:Cobalt; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005434:Flow Cytometry; D005562:Formazans; D005737:Garlic / Q000737:chemistry*; D016716:PC12 Cells; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000032:analysis; D013778:Tetrazolium Salts; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000975:Antioxidants; D051792:Basic Helix-Loop-Helix Proteins; D003035:Cobalt; D003545:Cysteine; D005562:Formazans; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D000099162:Endothelial PAS Domain-Containing Protein 1; C079782:MTT formazan; C065299:S-allylcysteine; C018021:cobaltous chloride
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