Analysis Tools
mortality/aging
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• following i.p. injection of a lethal dose of LPS, mice exhibit a significantly shorter median survival than LPS-injected wild-type controls (17 h versus 23 h, respectively)
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immune system
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• after LPS treatment, bone marrow-derived macrophages (BMDMs) show a significant increase in IL-6 secretion relative to LPS-treated wild-type BMDMs
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• after LPS treatment, BMDMs show a significant increase in TNF secretion relative to LPS-treated wild-type BMDMs
• 150 min after i.p. injection of LPS (35 ug/g of body weight) into mice, white blood cells (WBCs) show a significant increase in Tnf mRNA levels relative to cells from LPS-injected wild-type controls
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• following i.p. injection of a lethal dose of LPS, mice exhibit a significantly shorter median survival than LPS-injected wild-type controls (17 h versus 23 h, respectively)
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homeostasis/metabolism
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• BMDMs show a significant increase in TMED7 (transmembrane p24 trafficking protein 7) steady-state levels relative to wild-type BMDMs
• after LPS treatment, BMDMs show a 3-fold increase in RHBDD1 protein levels relative to LPS-treated wild-type BMDMs, indicating a negative feedback loop that increases RHBDD1 levels in response to LPS-induced TLR4 (toll-like receptor 4) signaling in macrophages
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• following i.p. injection of a lethal dose of LPS, mice exhibit a significantly shorter median survival than LPS-injected wild-type controls (17 h versus 23 h, respectively)
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liver/biliary system
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• at day 3 after i.p. injection of a sublethal dose of tunicamycin, livers are strikingly pale in color, indicating hepatic steatosis; Oil Red O staining showed massive accumulation of neutral lipids in liver relative to similarly treated wild-type controls
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growth/size/body
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• at day 3 after i.p. injection of a sublethal dose of tunicamycin, mice show a significantly greater weight loss than similarly treated wild-type controls
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cellular
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• after tunicamycin treatment (to induce ER stress), mouse embryonic fibroblasts (MEFs) derived from E14.5 embryos show abnormal redistribution of CKAP4 (cytoskeleton-associated protein 4, aka CLIMP-63) -- a marker for ER sheets -- with 28.76% of MEFs showing a collapse of CKAP4 signal around the nucleus rather than a wide spreading of CKAP4 throughout the cytoplasm as in wild-type MEFs; transient transfection with HA-tagged RHBDL4 WT significantly rescues ER morphology
• after exposure to nocodazole (to disrupt microtubules), MEFs show a less pronounced redistribution of CKAP4, with peripheral areas devoid of ER sheets in many cells, indicating defective microtubule-dependent ER sheet dynamics
• at day 1 after tunicamycin treatment, liver ER sheets are modestly but significantly narrower than in similarly treated wild-type livers; at day 3 post-treatment, the rough ER remains significantly dilated filling the cytoplasm, whereas wild-type liver ER sheets start to reassemble around mitochondria and show reduced luminal width, indicating recovery from ER stress
• MEFs show normal levels of ER-shaping proteins and the ER stress response and overall secretory function are similar to those in wild-type MEFs
• untreated MEFs exhibit normal ER sheet (CKAP4) distribution under normal conditions
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• at day 3 after i.p. injection of a sublethal tunicamycin dose, mice show a significantly greater weight loss and a dramatically higher lipid droplet accumulation in liver than similarly treated wild-type controls, indicating increased sensitivity to induced ER stress
• 3 days after tunicamycin treatment, the ER stress remains unresolved, as indicated by the persistence of the proapoptotic transcription factor CHOP and a significantly dilated rough ER, filling the cytoplasm, in liver tissue
• however, no defect in the activation of the unfolded protein response (UPR) is observed in response to ER stress
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