title: Curcumin-induced inhibition of proteasomal activity, enhanced HSP accumulation and the acquisition of thermotolerance in Xenopus laevis A6 cells.
abstract: In the present study, curcumin, a phenolic compound with anti-inflammatory, anti-tumor and anti-amyloid properties, inhibited proteasomal activity and induced the accumulation of HSPs in the frog model system, Xenopus laevis. Treatment of A6 kidney epithelial cells with curcumin enhanced ubiquitinated protein levels and inhibited chymotrypsin-like activity. Furthermore, exposure of cells to 10-50 μM curcumin for 24h induced HSP30 and HSP70 accumulation. This phenomenon was controlled at the transcriptional level since pre-treatment of cells with KNK437, a heat shock factor 1 (HSF1) inhibitor, repressed HSP accumulation. Additionally, elevation of the incubation temperature from 22 to 30 °C greatly enhanced the curcumin-induced accumulation of HSP30 and HSP70. Immunocytochemical analysis revealed that curcumin-induced HSP30 was detectable primarily in the cytoplasm in a punctate pattern with minimal detrimental effects on the actin cytoskeleton. Finally, prior exposure of cells to curcumin conferred a state of thermotolerance since it protected them against a subsequent cytotoxic thermal challenge. These findings are of importance given the interest in identifying agents that can upregulate HSP levels with minimal effects on cell structure or function as a therapeutic treatment of protein folding diseases.
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, ON, Canada N2L 3G1.
authors.forename: Saad
authors.initials: S
authors.lastname: Khan
authors.forename: John J
authors.initials: JJ
authors.lastname: Heikkila
mesh_terms: D000818:Animals; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D050890:HSP30 Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D018869:Heat-Shock Response; D006358:Hot Temperature; D011480:Protease Inhibitors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D004268:DNA-Binding Proteins; D050890:HSP30 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex; D003474:Curcumin