Molecular mechanism of induction of hemeoxygenase-1 by radiation, hyperthermia , and ultrasound

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For better understanding of the molecular mechanism of hemeoxygenase (HO)-1 as a component of cellular response to non-thermal low intensity pulsed ultrasound(LIPUS, 0.3 W/cm2 for 1 min), and mild hyperthermia (MH, 41℃, 30 min), we examined gene expression patterns and genetic networks in human lymphoma U937 cells using high-density oligonucleotide microarrays and computational gene expression analyses. Six hours after LIPUS treatment, apoptosis (14±3.8%) with no cell lysis was observed. Of 22,283 probe sets analyzed, LIPUS down-regulated 193 genes and up-regulated 201 genes by >1.5-fold. On the other hand, 423 genes were up-regulated and 515 genes were down-regulated in the cells 3 h post-treatment with MH which did not induce apoptosis. The significant genetic networks were identified and the interaction between HO-1 and NRG1 or NF2, and BCL2 or CREB1 was observed in the cells treated with LIPUS and MH, respectively. When the cells were exposed to X-rays, up-regulation of HO-1 was observed in 17937 cells but not in HeLa cells.The present results indicate that LIPUS and MH affect the expression of many genes and provide novel insight into the biomolecular mechanisms of HO-1. The identification of radiation-responsive genes interacting with HO-1 remains a subject for future studies.