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Gene interactions and pathways from curated databases and text-mining
Neuroscience 2005, PMID: 16111829

Differential involvement of p38 and JNK MAP kinases in HIV-1 Tat and gp120-induced apoptosis and neurite degeneration in striatal neurons.

Singh, I N; El-Hage, N; Campbell, M E; Lutz, S E; Knapp, P E; Nath, A; Hauser, K F

The role of p38 and c-jun-N-terminal kinases 1/2, members of the mitogen-activated protein kinase family, in mediating the toxic effects of human immunodeficiency virus-1 transactivator of transcription (Tat) and gp120 were explored in primary mouse striatal neurons in vitro. Both Tat and gp120 caused significant increases in p38 and c-jun-N-terminal kinase mitogen-activated protein kinase phosphorylation, caspase-3 activity, neurite losses and cell death in striatal neurons. Tat-induced increases in caspase-3 activity were significantly attenuated by an inhibitor of c-jun-N-terminal kinase (anthra[1,9-cd]pyrazol-6(2H)-one), but not by an inhibitor of p38 ([4-(4-fluorophenyl)-2-(4-methylsul-finylphenyl)-5-(4-pyridyl)1 H-imidazole]), mitogen-activated protein kinase. However, despite preventing increases in caspase-3 activity, c-jun-N-terminal kinase inhibition failed to avert Tat-induced neuronal losses suggesting that the reductions in caspase-3 activity were insufficient to prevent cell death caused by Tat. Alternatively, gp120-induced increases in caspase-3 activity, neurite losses and neuronal death were prevented by p38, but not c-jun-N-terminal kinase, mitogen-activated protein kinase inhibition. Our findings suggest that gp120 induces neuronal dysfunction and death through actions at p38 mitogen-activated protein kinase, while Tat kills neurons through actions that are independent of p38 or c-jun-N-terminal kinase mitogen-activated protein kinase, or through the concurrent activation of multiple proapoptotic pathways.

Diseases/Pathways annotated by Medline MESH: Nerve Degeneration
Document information provided by NCBI PubMed

Text Mining Data

Tat — p38: " Differential involvement of p38 and JNK MAP kinases in HIV-1 Tat and gp120 induced apoptosis and neurite degeneration in striatal neurons "

caspase-3 → Tat: " Both Tat and gp120 caused significant increases in p38 and c-jun-N-terminal kinase mitogen activated protein kinase phosphorylation, caspase-3 activity, neurite losses and cell death in striatal neurons "

caspase-3 → gp120: " Both Tat and gp120 caused significant increases in p38 and c-jun-N-terminal kinase mitogen activated protein kinase phosphorylation, caspase-3 activity, neurite losses and cell death in striatal neurons "

p38 → Tat: " Both Tat and gp120 caused significant increases in p38 and c-jun-N-terminal kinase mitogen activated protein kinase phosphorylation, caspase-3 activity, neurite losses and cell death in striatal neurons "

p38 → gp120: " Both Tat and gp120 caused significant increases in p38 and c-jun-N-terminal kinase mitogen activated protein kinase phosphorylation, caspase-3 activity, neurite losses and cell death in striatal neurons "

caspase-3 → Tat: " Tat induced increases in caspase-3 activity were significantly attenuated by an inhibitor of c-jun-N-terminal kinase ( anthra [ 1,9-cd ] pyrazol-6 ( 2H ) -one ), but not by an inhibitor of p38 ( [ 4- ( 4-fluorophenyl ) -2- ( 4-methylsul-finylphenyl ) -5- ( 4-pyridyl ) 1 H-imidazole ] ), mitogen activated protein kinase "

caspase-3 → p38: " Tat induced increases in caspase-3 activity were significantly attenuated by an inhibitor of c-jun-N-terminal kinase ( anthra [ 1,9-cd ] pyrazol-6 ( 2H ) -one ), but not by an inhibitor of p38 ( [ 4- ( 4-fluorophenyl ) -2- ( 4-methylsul-finylphenyl ) -5- ( 4-pyridyl ) 1 H-imidazole ] ), mitogen activated protein kinase "

caspase-3 ⊣ p38: " Alternatively, gp120 induced increases in caspase-3 activity, neurite losses and neuronal death were prevented by p38 , but not c-jun-N-terminal kinase, mitogen activated protein kinase inhibition "

caspase-3 → gp120: " Alternatively, gp120 induced increases in caspase-3 activity, neurite losses and neuronal death were prevented by p38, but not c-jun-N-terminal kinase, mitogen activated protein kinase inhibition "

mitogen activated protein kinase → p38: " Alternatively, gp120 induced increases in caspase-3 activity, neurite losses and neuronal death were prevented by p38 , but not c-jun-N-terminal kinase, mitogen activated protein kinase inhibition "

Manually curated Databases

No curated data.