title: Down-regulation of heat shock protein HSP90ab1 in radiation-damaged lung cells other than mast cells.
abstract: Ionizing radiation (IR) leads to fibrosing alveolitis (FA) after a lag period of several weeks to months. In a rat model, FA starts at 8 weeks after IR. Before that, at 5.5 weeks after IR, the transcription factors Sp1 (stimulating protein 1) and AP-1 (activator protein 1) are inactivated. To find genes/proteins that were down-regulated at that time, differentially expressed genes were identified in a subtractive cDNA library and verified by quantitative RT-PCR (reverse transcriptase polymerase chain reaction), western blotting and immunohistochemistry (IH). The mRNA of the molecular chaperone HSP90AB1 (heat shock protein 90 kDa alpha, class B member 1) was down-regulated 5.5 weeks after IR. Later, when FA manifested, HSP90ab1 protein was down-regulated by more than 90% in lung cells with the exception of mast cells. In most mast cells of the normal lung, both HSP90ab1 and HSP70, another major HSP, show a very low level of expression. HSP70 was massively up-regulated in all mast cells three months after irradiation whereas HSP90AB1 was up-regulated only in a portion of mast cells. The strong changes in the expression of central molecular chaperones may contribute to the well-known disturbance of cellular functions in radiation-damaged lung tissue.
authors.affiliation: Department of Pediatric Surgery (MGH, GF), University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Haase
authors.forename: Peter
authors.initials: P
authors.lastname: Geyer
authors.forename: Guido
authors.initials: G
authors.lastname: Fitze
authors.forename: Gustavo B
authors.initials: GB
authors.lastname: Baretton
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015536:Down-Regulation; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects*; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human; D012333:RNA, Messenger
keywords: HSP70; HSP90ab1; fibrosing alveolitis; heat shock protein; mast cells; radiation damage