Heat shock cellular stress on aged gut-associated lymphocytes; mRNA expression of inducible heat shock protein gene and protooncogenes.
To investigate the effects of senescence and cellular stress on gut mucosal lymphocytes, we used heat shock (HS) to determine the mRNA expression of an inducible HSP70-family gene (HSP68) and two nuclear protooncogenes (c-fos and c-myc) from gut-associated (GA) lymphocytes of aged (> or = 24 month) and young (3-4 month) mice. First, with temperatures of 37-44 degrees C, the maximal HS effect on expression of inducible HSP68 mRNA was at 41 degrees C, and that of c-fos and c-myc at 42 degrees C; with HS durations of 0-6 h at 42 degrees C, the maximal effect was at 1 or 2 h in the young GA lymphocytes. Second, without HS (37 degrees C), inducible HSP68 mRNA was not expressed in the GA lymphocytes of both age groups. The expression of c-fos and c-myc mRNA was greater in the aged GA lymphocytes than in the young, and c-myc mRNA was more highly expressed than c-fos mRNA in both age groups. Third, with HS (42 degrees C) for 30 min to 6 h, followed by recovery (37 degrees C) for up to 6 h, the peak expression of inducible HSP68 mRNA in the aged GA lymphocytes was reduced, but occurred at the same time as seen in the young (2 h) and declined faster during the recovery period. The peak expression of c-fos mRNA in the aged GA lymphocytes was earlier than that of the HSP68 mRNA in both age groups (1 h); the intensity of expression was decreased at all time points in the aged and declined more rapidly during the recovery period, whereas the peak expression of c-myc mRNA in the aged GA lymphocytes after HS was retarded in time (2 h) but also reduced in amount, when compared to that of the young, and during recovery the expression declined more rapidly in the aged than in the young. However, the recovery kinetics of the above three mRNAs remained unaltered in the lymphocytes from two different ages. To summarize our conclusions: First, prior to HS cellular stress, aged GA lymphocytes did not show mRNA expression of HSP68 but augmented mRNA expression of the nucleoprotooncogenes c-fos and c-myc. These findings suggest that senescent lymphocytes are more active metabolically in vivo than are young ones without significant activation of an inducible HSP70 family gene.(ABSTRACT TRUNCATED AT 400 WORDS)
Kawanishi
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Gut Mucosal Molecular Immunology Laboratory, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903-0019.
Fujioka
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D000375:Aging / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D016762:Genes, fos; D016259:Genes, myc; D006360:Heat-Shock Proteins / Q000235:genetics*; D006358:Hot Temperature; D007422:Intestines / Q000276:immunology; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis*
D006360:Heat-Shock Proteins; D012333:RNA, Messenger