Proteasome inhibition increases HuR level, restores heat-inducible HSP72 expression and thermotolerance in WI-38 senescent human fibroblasts.
At the end of their replicative potential in vitro, late passage WI-38 human diploid fibroblasts (HDF) have a low basal expression of heat shock protein 72 (HSP72) and an attenuated ability to induce it in response to heat shock. The transient exposure to the specific and reversible proteasome inhibitor MG132 during a mild heat shock induced late passage HDF to synthesize and accumulate high levels of HSP72. This HSP72 expression was long-lasting and appeared to result from both increased cytoplasmic levels and enhanced translation of HSP72 mRNA. The level of HuR, a stabilizing mRNA-binding protein, increased following the MG132 treatment. This result is consistent with the proposed role of HuR in assisting mRNA export to the cytoplasm and in antagonizing its degradation. Furthermore, the previous exposure of late passage HDF to a mild heat shock in the presence of MG132 protected these cells against the otherwise lethal effect of a subsequent severe heat shock. This acquisition of thermotolerance appeared to be correlated with the level of HSP72.
Bonelli
Mara A
MA
Sezione di Patologia Molecolare e Immunologia, Dipartimento di Medicina Sperimentale, Università degli Studi di Parma, Via Volturno 39, 43100 Parma, Italy.
Alfieri
Roberta R
RR
Desenzani
Silvia
S
Petronini
Pier Giorgio
PG
Borghetti
Angelo F
AF
D000954:Antigens, Surface / Q000032:analysis / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D008168:Lung / Q000196:embryology; D011480:Protease Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D014157:Transcription Factors
D000954:Antigens, Surface; D004268:DNA-Binding Proteins; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D050884:HSP72 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D007976:Leupeptins; D011480:Protease Inhibitors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde