Heat shock - induced Hsp70 expression in murine astrocytes does not require poly(ADP-ribose) polymerase activity.
Poly(ADP-ribose) polymerase (PARP) activity is involved in DNA repair, replication, recombination, and transcription. Extensive activation of the most abundant PARP, PARP-1, during ischemia or inflammation can promote cell death. PARP inhibitors reduce this cell death and are currently under investigation for use as therapeutic agents. A recent study found that PARP activation was required for Hsp70 upregulation in heat-exposed Drosophila larvae. Here we sought to determine whether PARP activity is likewise required for Hsp70 upregulation in mammalian cells, since many of the settings in which PARP inhibitors are candidate therapeutic agents are also settings in which Hsp70 expression is an important component of the stress response. We examined this issue using murine astrocyte cultures, a mammalian preparation in which the Hsp70 response has been well characterized, and found that PARP inhibitors had no effect on heat shock-induced Hsp70 protein expression. PARP-1(-/-) astrocytes gave similar results. The present findings indicate that PARP activity, and specifically PARP-1, is not required for upregulation of Hsp70 expression in mammalian cells.Basel
Department of Neurology, University of California at San Francisco and Veterans Affairs Medical Center, San Francisco, CA 94121-1545, USA.
Mary
M
Sevigny
Philippe
P
Garnier
Tiina
T
Kauppinen
Raymond
R
Swanson
D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D018869:Heat-Shock Response; D051379:Mice; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D015854:Up-Regulation
D018840:HSP70 Heat-Shock Proteins; D011065:Poly(ADP-ribose) Polymerases