Quinolinic acid selectively induces apoptosis of human astrocytes: potential role in AIDS dementia complex

Journal of Neuroinflammation

Bruce J Brew¹  Lily Wang²  Gilles J Guillemin³ 

[1] Department of Neurology, St Vincent's Hospital, Sydney, Australia;Centre for Immunology, St Vincent's Hospital, Sydney, Australia;University of New South Wales, Faculty of Medicine, Sydney, Australia

关键词: AIDS dementia complex;    caspase 3;    quinolinic acid;    apoptosis;    astrocyte;    Human;   

Others  :  1213667
DOI  :  10.1186/1742-2094-2-16

 received in 2005-03-02, accepted in 2005-07-26,  发布年份 2005

【 摘 要 】

There is evidence that the kynurenine pathway (KP) and particularly one of its end products, quinolinic acid (QUIN) play a role in the pathogenesis of several major neuroinflammatory diseases, and more particularly AIDS dementia complex (ADC). We hypothesized that QUIN may be involved in astrocyte apoptosis because: 1) apoptotic astrocytes have been observed in the brains of ADC patients, 2) ADC patients have elevated cerebrospinal fluid QUIN concentrations, and 3) QUIN can induce astrocyte death. Primary cultures of human fetal astrocytes were treated with three pathophysiological concentrations of QUIN. Numeration of apoptotic cells was assessed using double immunocytochemistry for expression of active caspase 3 and for nucleus condensation. We found that treatment of human astrocytes with QUIN induced morphological (cell body shrinking) and biochemical changes (nucleus condensation and over-expression of active caspase 3) of apoptosis. After 24 hours of treatment with QUIN 500 nM and 1200 nM respectively 10 and 14% of astrocytes were undergoing apoptosis. This would be expected to lead to a relative lack of trophic support factors with consequent neuronal dysfunction and possibly death. Astroglial apoptosis induced by QUIN provides another potential mechanism for the neurotoxicity of QUIN during ADC.

【 授权许可】

   
2005 Guillemin et al; licensee BioMed Central Ltd.

【 图 表 】

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