Highlights ► Mechanical loading to the tibia decreases integrated stress responses. ► Hindlimb unloading increases integrated stress responses in the tibia. ► A release from hindlimb unloading reduces integrated stress responses. ► A return to Earth gravity from space suppresses integrated stress responses. ► A period of 2–4h is sufficient to induce this suppressive outcome.

    Abstract Various environmental stresses elevate the phosphorylation level of eukaryotic translation initiation factor 2 alpha (eIF2α) and induce transcriptional activation of a set of stress responsive genes such as activating transcription factors 3 and 6 (ATF3 and ATF6), CCAAT/enhancer-binding protein homologous protein (CHOP), and Xbp1 (X-box binding protein 1). These stress sources include radiation, oxidation, and stress to the endoplasmic reticulum, and it is recently reported that unloading by hindlimb unloading is such a stress source. No studies, however, have examined the phosphorylation level of eIF2α (eIF2α-p) using skeletal samples that have experienced microgravity in space. In this study we addressed a question: Does a mouse tibia flown in space show altered levels of eIF2α-p? To address this question, we obtained STS-135 flown samples that were harvested 4–7h after landing. The tibia and femur isolated from hindlimb unloaded mice were employed as non-flight controls. The effects of loading were also investigated in non- flight controls. Results indicate that the level of eIF2α-p of the non-flight controls was elevated during hindlimb unloading and reduced after being released from unloading. Second, the eIF2α-p level of space-flown samples was decreased, and mechanical loading to the tibia caused the reduction of the eIF2α-p level. Third, the mRNA levels of ATF3, ATF6, and CHOP were lowered in space-flown samples as well as in the non-flight samples 4–7h after being released from unloading. Collectively, the results herein indicated that a release from hindlimb unloading and a return to normal weight environment from space provided a suppressive effect to eIF2α-linked stress responses and that a period of 2–4h is sufficient to induce this suppressive outcome.


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    Title :

    Regulation of eIF2α phosphorylation in hindlimb-unloaded and STS-135 space-flown mice


    Contributors:

    Published in:

    Advances in Space Research ; 50 , 5 ; 576-583


    Publication date :

    2012-05-26


    Size :

    8 pages




    Type of media :

    Article (Journal)


    Type of material :

    Electronic Resource


    Language :

    English





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