Cytoprotection against thermal injury: evaluation of herbimycin A by cell viability and cDNA arrays.
Herbimycin A (HA), a known inducer of the heat shock response, was investigated for its ability to increase survival of a human cell line following thermal injury. Its effect on transcriptional activity was also assessed with cDNA arrays to provide new targets for cytoprotection. Pretreatment with at least 0.75 microg/ml HA significantly increased the fraction of cells surviving thermal injury by up to 50% (based on 8s exposure) compared to untreated controls. HA also significantly induced transcription of mRNA for HSP90 and HSP70, and protein production for HSP40 and HSP70. Gene expression profiling demonstrated that the most highly elevated genes included growth factors and transcription factors, while prominently suppressed genes included transcription factors and kinases. These results suggest that cytoprotection may be due to the contribution of the products of a significant number of genes in addition to the classic stress response genes, suggesting that modulation of these genes might induce thermotolerance and amelioration of thermal injury.
Dinh
H K
HK
Division of Pharmaceutics, The University of Texas at Austin, Austin, TX, USA.
Stavchansky
S
S
Schuschereba
S T
ST
Stuck
B E
BE
Bowman
P D
PD
D016227:Benzoquinones; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D018076:DNA, Complementary / Q000096:biosynthesis; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D047029:Lactams, Macrocyclic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data; D011809:Quinones / Q000494:pharmacology* / Q000627:therapeutic use; D017828:Rifabutin / Q000031:analogs & derivatives
D016227:Benzoquinones; D018076:DNA, Complementary; D006360:Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin