title: Chemical inducers of heat shock proteins derived from medicinal plants and cytoprotective genes response.
abstract: Environmental stress induces damage that activates an adaptive response in any organism. The cellular stress response is based on the induction of cytoprotective proteins, the so-called stress or heat shock proteins (HSPs). HSPs are known to function as molecular chaperones which are involved in the therapeutic approach of many diseases. Therefore in the current study we searched nontoxic chaperone inducers in chemical compounds isolated from medicinal plants. Screening of 80 compounds for their Hsp70-inducing activity in human lymphoma U937 cells was performed by western blotting. Five compounds showed significant Hsp70 up-regulation among them shikonin was most potent. Shikonin was able to induce Hsp70 at 0.1 µM after 3 h without activation of heat shock transcription factor 1 (HSF-1). It also induces significant reactive oxygen species generation. The expression level of genes responsive to shikonin was studied using global-scale microarrays and computational gene expression analysis tools. Significant increase in the nuclear factor erythroid 2-related factor 2 (Nrf2, NFEL2L2) -mediated oxidative stress response was observed that leads to the activation of HSP. The results of gene chip analysis were further confirmed by real-time qPCR assay. In short, the detailed mechanisms of Hsp70 induction by shikonin is not fully understood, Nrf2 and its target genes might be involved in the Hsp70 up-regulation in U937 cells.
authors.affiliation: Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
authors.forename: Kanwal
authors.initials: K
authors.lastname: Ahmed
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Furusawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tabuchi
authors.forename: Heba F
authors.initials: HF
authors.lastname: Emam
authors.forename: Jin-Lan
authors.initials: JL
authors.lastname: Piao
authors.forename: Mariame Ali
authors.initials: MA
authors.lastname: Hassan
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Makoto
authors.initials: M
authors.lastname: Kadowaki
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D009285:Naphthoquinones / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010946:Plants, Medicinal; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020298:U937 Cells
chemical_list: D004365:Drugs, Chinese Herbal; D006360:Heat-Shock Proteins; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; C016101:shikonin