Aluminum Maltolate-Induced Cytotoxicity in Neuro-2a Cells Involves Apoptosis and Necrosis

Details

• Personal Author:
  Johnson VJ ; Sharma RP
• Description:
  Aluminum maltolate (Al-malt) has been shown to cause neurodegeneration following in-vivo exposure and apoptosis plays a prominent role. The objective of this study was to define the mode of cell death induced by Al-malt. Neuro-2a cells were treated with Al-malt for 24 h in the presence or absence of pretreatment with a variety of pharmacological agents. Al-malt concentration-dependently increased cell death as indicated by lactate dehydrogenase (LDH) release and the appearance of cells with hypodiploid DNA content. Flow cytometry using acridine orange (high-live, low-apoptotic) and ethidium bromide (necrotic) dual staining showed that the mode of cell death was a combination of apoptosis and necrosis. Treatment with Al-malt resulted in caspase 3 activation and the externalization of phosphatidyl serine, both indicative of apoptosis. In addition, nuclear condensation and fragmentation were evident in Hoechst 33258 stained nuclei from Al-malt-treated cultures. Interestingly, pretreatment with cyclohexamide (CHX) markedly reduced Al-malt-induced apoptosis indicating that this mode of death is dependent on de-novo protein synthesis in the current culture model. Necrotic cell death was not prevented by CHX suggesting that only apoptosis was dependent on gene expression. Pretreatment with antioxidants and kinase inhibitors (mitogen activated protein kinases and PKC) did not reduce Al-malt toxicity suggesting independence from oxidative stress and major kinase signaling pathways. The results provide insight into the mechanisms of Al-malt neurotoxicity and support the involvement of this metal in neurodegeneration. [Description provided by NIOSH]
• Subjects:
  Aluminum Compounds Metals Nervous System Occupational Health Poisoning Safety
• Keywords:
  Aluminum-compounds Cell-damage Cellular-reactions In-vitro-studies Metal-compounds Metal-poisoning Neurotoxic-effects Neurotoxicity Neurotoxicology
• ISSN:
  1096-6080
• Publisher:
  Society of Toxicology
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  23
• Volume:
  72
• NIOSHTIC Number:
  nn:20022526
• Citation:
  Toxicologist 2003 Mar; 72(S-1):23
• CAS Registry Number:
  Tris[3-(hydroxy-κO)-2-methyl-4H-pyran-4-onato-κO4]aluminum (CAS RN 23058-19-7)
• Federal Fiscal Year:
  2003
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah
• Supplement:
  S-1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ff06c2e6741239d886487c52cd2ec3599abc34f3f21f5e601a472f3fbc8e7773b191f2c4a15c91446f3346c94d4b259ac39a5edeaef3ff15cdaf58b9ca59e8ec
• Download URL:
  https://stacks.cdc.gov/view/cdc/199272/cdc_199272_DS1.pdf
• File Type:
  [PDF - 56.41 KB ]