Journal article
Apoptotic and Antiapoptotic Effects of CXCR4: Is It a Matter of Intrinsic Efficacy? Implications for HIV Neuropathogenesis
AIDS research and human retroviruses, v 20(10), pp 1063-1071
Oct 2004
PMID: 15585097
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
CXCR4, the specific receptor for the chemokine SDF-1
α
that also binds CXCR4-using HIV gp120s, affects survival of different cell types, including neurons. However, current data show that the outcome of CXCR4 activation on neuronal survival may vary depending on the ligand and/or the cellular conditions. In this study, we have systematically compared the effects of SDF-1
α
and gp120
IIIB
(with or without CD4) on several intracellular pathways involved in cell survival, including MAP kinases and Akt-dependent pathways. Our data show that gp120
IIIB
and SDF-1
α
are both potent activators of MAP kinases in neuronal and non-neuronal cells, though the kinetic of these responses is slightly different. Furthermore, unlike SDF-1
α
, and independently of CD4, gp120
IIIB
is unable to stimulate Akt and some of its antiapoptotic targets (NF-
κ
B and MDM2)—despite its ability to activate other signaling pathways in the same conditions. Finally, the viral protein is more efficient in recruiting some effectors (e.g., JNK) than others in comparison with SDF-1
α
(EC
50
= 0.1 vs. 0.6 nM). We conclude that the intrinsic efficacy of the two ligands is significantly different and is pathway dependent. These findings have important implications for our understanding of CXCR4-mediated responses in the CNS, as well as the role of this coreceptor in HIV neuropathogenesis.
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Details
- Title
- Apoptotic and Antiapoptotic Effects of CXCR4: Is It a Matter of Intrinsic Efficacy? Implications for HIV Neuropathogenesis
- Creators
- MUHAMMAD Z KHAN - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102RENATO BRANDIMARTI - Department of Experimental Pathology, University of Bologna, Bologna 40126, ItalyJEEGAR P PATEL - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102NHA HUYNH - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102JUN WANG - Department of Biochemistry and Chemistry, University of Illinois, Urbana–Champaign, Champaign, Illinois 61801ZIWEI HUANG - Department of Biochemistry and Chemistry, University of Illinois, Urbana–Champaign, Champaign, Illinois 61801ALESSANDRO FATATIS - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102OLIMPIA MEUCCI - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102
- Publication Details
- AIDS research and human retroviruses, v 20(10), pp 1063-1071
- Publisher
- Mary Ann Liebert
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000224546900005
- Scopus ID
- 2-s2.0-6344269072
- Other Identifier
- 991014878226704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Infectious Diseases
- Virology