Aluminum maltolate-induced toxicity in NT2 cells occurs through apoptosis and includes cytochrome c release.

نویسندگان

  • Kathleen J S Griffioen
  • Othman Ghribi
  • Nena Fox
  • John Savory
  • David A DeWitt
چکیده

Aluminum (Al) compounds are neurotoxic and have been shown to induce experimental neurodegeneration although the mechanism of this effect is unclear. In order to study this neurotoxic effect of Al, we have developed an in vitro model system using Al maltolate and human NT2 cells. Al maltolate at 500 microM caused significant cell death with a 24-h incubation and this toxicity was even more evident after 48 h. Lower doses of Al maltolate were also effective, but required a longer incubation for cell death. Nuclear fragmentation suggestive of apoptosis was observed as early as three hours and increased substantially through 24 h. Chromatin condensation and nuclear fragmentation were confirmed by electron microscopy. In addition, TUNEL positive nuclei were also observed. The release of cytochrome c was demonstrated with Western blot analysis. This in vitro model using human cells adds to our understanding of Al neurotoxicity and could provide insight into the neurodegenerative processes in human disease.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Peri-nuclear clustering of mitochondria is triggered during aluminum maltolate induced apoptosis.

Synapse loss and neuronal death are key features of Alzheimer's disease pathology. Disrupted axonal transport of mitochondria is a potential mechanism that could contribute to both. As the major producer of ATP in the cell, transport of mitochondria to the synapse is required for synapse maintenance. However, mitochondria also play an important role in the regulation of apoptosis. Investigation...

متن کامل

The Hydroalcoholic Extract of Saffron Protects PC12 Cells against Aluminum-Induced Cell Death and Oxidative Stress in Vitro

Background: Aluminum (Al) exposure is among the environmental risk factors that may involve in the pathogenesis of neurodegenerative diseases. Oxidative stress has a critical role in the Al-induced toxicity. Saffron is a plant with potent radical scavenging and anti-oxidative properties. This investigation was designed to evaluate the possible protective effects of saffron extract (SE) on alumi...

متن کامل

Cytochrome C and Caspase-3/7 are Involved in Mycophenolic Acid-induced Apoptosis in Genetically Engineered PC12 Neuronal Cells Expressing the p53 Gene

Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil. This study designed to investigate the mechanism of cytotoxicity of MPA on the genetically engineered PC12 Tet Off (PTO) neuronal cells with p53 gene. Alamar Blue (AB) reduction showed concentration-dependent cytotoxicity of MPA on PTO cells with IC50 value of 32.32 ± 4.61 mM. The reactive oxygen species (ROS) generation...

متن کامل

Cytochrome C and Caspase-3/7 are Involved in Mycophenolic Acid-induced Apoptosis in Genetically Engineered PC12 Neuronal Cells Expressing the p53 Gene

Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil. This study designed to investigate the mechanism of cytotoxicity of MPA on the genetically engineered PC12 Tet Off (PTO) neuronal cells with p53 gene. Alamar Blue (AB) reduction showed concentration-dependent cytotoxicity of MPA on PTO cells with IC50 value of 32.32 ± 4.61 mM. The reactive oxygen species (ROS) generation...

متن کامل

Protective effects of nimodipine and lithium against aluminum-induced cell death and oxidative stress in PC12 cells

Objective(s): The role of aluminum (Al) in the pathogenesis of neurodegenerative diseases has been implicated in several studies. However, the exact mechanisms of cytotoxic effects of Al have not been elucidated yet. The aim of this study was to investigate the effect of L-type calcium channel antagonist, nimodipine (NM), and lithium chloride (LiCl) on Al-induced toxicity in PC12 cells. Materia...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Neurotoxicology

دوره 25 5  شماره 

صفحات  -

تاریخ انتشار 2004