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PMID:12753088

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Citation

Eugenin, EA, D'Aversa, TG, Lopez, L, Calderon, TM and Berman, JW (2003) MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis. J. Neurochem. 85:1299-311

Abstract

Acquired immunodeficiency syndrome (AIDS)-associated dementia is often characterized by chronic inflammation, with infected macrophage infiltration of the CNS resulting in the production of human immunodeficiency virus type 1 (HIV-1) products, including tat, and neurotoxins that contribute to neuronal loss. In addition to their established role in leukocyte recruitment and activation, we identified an additional role for chemokines in the CNS. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and regulated upon activation normal T cell expressed and secreted (RANTES) were found to protect mixed cultures of human neurons and astrocytes from tat or NMDA-induced apoptosis. Neuronal and astrocytic apoptosis in these cultures was significantly inhibited by co-treatment with MCP-1 or RANTES but not IP-10. The protective effect of RANTES was blocked by antibodies to MCP-1, indicating that RANTES protection is mediated by the induction of MCP-1. The NMDA blocker, MK801, also abolished the toxic effects of both tat and NMDA. Tat or NMDA treatment of mixed cultures for 24 h resulted in increased extracellular glutamate ([Glu]e) and NMDA receptor 1 (NMDAR1) expression, potential contributors to apoptosis. Co-treatment with MCP-1 inhibited tat and NMDA-induced increases in [Glu]e and NMDAR1, and also reduced the levels and number of neurons containing intracellular tat. These data indicate that MCP-1 may play a novel role as a protective agent against the toxic effects of glutamate and tat.

Links

PubMed

Keywords

AIDS Dementia Complex/metabolism; Apoptosis/drug effects; Astrocytes/cytology; Astrocytes/drug effects; Astrocytes/physiology; Cells, Cultured; Chemokine CCL2/pharmacology; Chemokine CCL5/pharmacology; Coculture Techniques; Dizocilpine Maleate/pharmacology; Excitatory Amino Acid Antagonists/pharmacology; Gene Products, tat/toxicity; Glutamic Acid/metabolism; Humans; N-Methylaspartate/toxicity; Neurons/cytology; Neurons/drug effects; Neurons/physiology; Neuroprotective Agents/pharmacology; Receptors, N-Methyl-D-Aspartate/metabolism; tat Gene Products, Human Immunodeficiency Virus

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CCL2

involved_in

GO:0034351: negative regulation of glial cell apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CCL2

involved_in

GO:0043524: negative regulation of neuron apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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