title: Heat acclimation memory: do the kinetics of the deacclimated transcriptome predispose to rapid reacclimation and cytoprotection?
abstract: Faster reinduction of heat acclimation (AC) after its decline indicates "AC memory." Our previous results revealed involvement of epigenetic mechanisms of transcriptional regulation. We hypothesized that the decline of AC (DeAC) is a period of "dormant memory" during which many processes are alerted to enable rapid reacclimation (ReAC). Using a genomewide approach we studied the AC, DeAC, and ReAC transcriptomes, to uncover hallmark pathways linked to "molecular memory" in the cardioacclimatome. Fifty rats subjected to heat acclimation [34°C for 2d (AC2d) or 30d (AC30)], DeAC (24°C, 30 days), ReAC (34°C, 2 days), and untreated controls were used. The GeneChip Rat Gene 1.0 ST Array was employed for left ventricular (cardiac) mRNA hybridization. Three independent bioinformatic analyses showed that 1) during AC2d enrichment of DNA impair/repair-linked genes is seen, and this is the molecular on-switch of acclimation; 2) genes activated in AC30 underlie the qualitative physiological adaptations of cardiac performance; 3) particular molecular programs encompassing constitutive upregulation of p38 MAPK, Jak/Stat, and Akt pathways and targets are specifically activated during DeAC and ReAC; and 4) epigenetic markers such as linker histones (histones H1 cluster), associated with nucleosome spacing, transcriptional chromatin modifiers, poly-(ADP-ribose) polymerase-1 (PARP1) linked to chromatin compaction, and microRNAs are only altered during DeAC/ReAC. The latter are newcomers to the AC/DeAC puzzle. We suggest that these transcriptional responses maintain euchromatin and proteostasis and enable faster physiological recovery upon ReAC by rapidly reestablishing the protected acclimated cardiophenotype. We propose that the cardiac AC model can be applied to acclimation processes in general.
authors.affiliation: Laboratory of Environmental Physiology, Faculty of Dentistry, The Hebrew University, Jerusalem, Israel; and.
authors.forename: Anna
authors.initials: A
authors.lastname: Tetievsky
authors.affiliation: Laboratory of Environmental Physiology, Faculty of Dentistry, The Hebrew University, Jerusalem, Israel; and.
authors.forename: Miri
authors.initials: M
authors.lastname: Assayag
authors.affiliation: The Mina and Everard Goodman Faculty of Life Science Bar Ilan University, Ramat Gan, Israel.
authors.forename: Rotem
authors.initials: R
authors.lastname: Ben-Hamo
authors.affiliation: The Mina and Everard Goodman Faculty of Life Science Bar Ilan University, Ramat Gan, Israel.
authors.forename: Sol
authors.initials: S
authors.lastname: Efroni
authors.affiliation: Laboratory of Environmental Physiology, Faculty of Dentistry, The Hebrew University, Jerusalem, Israel; and.
authors.forename: Gal
authors.initials: G
authors.lastname: Cohen
authors.affiliation: Laboratory of Environmental Physiology, Faculty of Dentistry, The Hebrew University, Jerusalem, Israel; and.
authors.forename: Atallah
authors.initials: A
authors.lastname: Abbas
authors.affiliation: Laboratory of Environmental Physiology, Faculty of Dentistry, The Hebrew University, Jerusalem, Israel; and m.horowitz@mail.huji.ac.il.
authors.forename: Michal
authors.initials: M
authors.lastname: Horowitz
mesh_terms: D000064:Acclimatization; D000818:Animals; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006321:Heart / Q000502:physiology*; D006358:Hot Temperature; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011897:Random Allocation; D051381:Rats; D059467:Transcriptome
keywords: adaptive memory; cardiotranscriptome; epigenetic markers; heat-acclimation/deacclimation/reacclimation