title: The role of local renin-angiotensin system on high glucose-induced cell toxicity, apoptosis and reactive oxygen species production in PC12 cells.
abstract: OBJECTIVE
  Hyperglycemia, oxidative stress and apoptosis have key roles in pathogenesis of diabetic neuropathy. There are local renin-angiotensin systems (RASs) in different tissues such as neural tissue. Local RASs are involved in physiological and pathophysiological processes such as inflammation, proliferation and apoptosis. This study aimed to investigate the role of local renin-angiotensin system on high glucose-induced cell toxicity, apoptosis and reactive oxygen species (ROS) production in PC12 cells, as a cell model of diabetic neuropathy.
  
  
  METHODS
  PC12 cells were exposed to a high glucose concentration (27 mg/ml), captopril (ACE inhibitor), telmisartan and losartan (AT1 antagonists), and also PD123319 (AT2 antagonist) were administered before and after induction of high glucose toxicity. Then cell viability was assessed by MTT assay and apoptotic cells and intracellular ROS production were detected by annexin V-propidium iodide and DCFDA, respectively, using flow cytometry.
  
  
  RESULTS
  High glucose concentration decreased cell viability, and increased apoptotic cells. Intracellular ROS production was also increased. In PC12 cells pretreatment and treatment by the drugs showed a significant improvement in cell viability and reduced apoptosis in captopril, telmisartan and PD123319 but only captopril and telmisartan were able to reduce ROS production. Losrtan significantly lowered ROS but didn't show any improvements in cell viability and apoptotic cells.
  
  
  CONCLUSIONS
  The results of the present study showed that RAS inhibitors reduced cell toxicity and apoptosis and ROS production was induced by high glucose. It may be suggested that local RAS has a role in high glucose toxicity.
authors.affiliation: Neurocognitive Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran ; Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Kaveh
authors.initials: K
authors.lastname: Shahveisi
authors.affiliation: Pharmacological Research Center of Medicinal Plants and Department of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Hadi
authors.initials: SH
authors.lastname: Mousavi
authors.affiliation: Neurocognitive Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Hosseini
authors.affiliation: Applied Physiology Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Abolfazl Khajavi
authors.initials: AK
authors.lastname: Rad
authors.affiliation: Immunogenetic and Cell Culture Department, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran ; North Khorasan University of Medical Sciences, Bojnurd, Iran.
authors.forename: Seyed Amir
authors.initials: SA
authors.lastname: Jalali
authors.affiliation: Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Ziba
authors.initials: Z
authors.lastname: Rajaei
authors.affiliation: Neurocognitive Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran ; Pharmacological Research Center of Medicinal Plants and Department of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Sadeghnia
authors.affiliation: Neurocognitive Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran ; Applied Physiology Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mousa-Al-Reza
authors.initials: MA
authors.lastname: Hadjzadeh
keywords: Apoptosis; High glucose toxicity; Oxidative stress; PC12; Renin-angiotensin system