Lipopolysaccharide Induces Cyp2E1 in Astrocytes Through Map Kinase Kinase-3 and C/Ebp/Β and -Δ

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Supplementary Material for: Aromatase/Seladin-1 Interactions in Human Neuronal Cell Culture, the Hippocampus of Healthy Rats and Transgenic Alzheimer’s Disease Mice

<b><i>Background/Aims:</i></b> Decreasing levels of aromatase and seladin-1 could be one of the molecular mechanisms of Alzheimer’s disease (AD). Aromatase is an enzyme that catalyzes estrogen biosynthesis from androgen precursors, and seladin-1 is an enzyme that converts desmosterol to cholesterol, which is the precursor of all hormones. Verifying the potential relationship between these proteins and accordingly determining new therapeutic targets constitute the aims of this study. <b><i>Methods:</i></b> Changes in protein levels were compared in vitro in aromatase and seladin-1 inhibitor-administered human neuroblastoma (SH-SY5Y) cells in vivo in intracerebroventricular (icv) aromatase or seladin-1 inhibitor-administered rats, as well as in transgenic AD mice in which the genes encoding these proteins were knocked out. <b><i>Results and Conclusions:</i></b> In the cell cultures, we observed that seladin-1 protein levels increased after aromatase enzyme inhibition. The hippocampal aromatase protein levels decreased following chronic seladin-1 inhibition in icv inhibitor-administered rats; however, the aromatase levels in the dentate gyrus of seladin-1 knockout (SelKO) AD male mice increased. These findings indicate a partial relationship between these proteins and their roles in AD pathology

Aromatase and C/EBP expression after global ischemia/reperfusion injury in rat hippocampus

Background and aims: Global ischemia after cardiac arrest, intraoperative hypoxia/hypotension, or hemorrhagic shock is one of the causes of brain injury, resulting in severe neurological and neurobehavioral deficit. Since neurodegeneration can be protected from by local aromatase expression and estrogen synthesis can be neuroprotective in the ischemia/reperfusion process, aromatase may be a potential target to study reperfusion injury after brain ischemia. We investigated the expression of aromatase and C/EBP by using Western blotting in rat hippocampus after transient global ischemia + hypotension (CAO + jvht). Methods: Transient two vessel occlusion global ischemia plus hypotension was produced. Briefly, animals were anesthetized and body temperature maintained within the normal range (37.0–37.5 °C), throughout the experiment. The femoral artery was exposed and catheterized to allow continuous recording of arterial blood. Bilateral common carotid arteries were temporarily occluded (CAO), and blood was gradually withdrawn from the jugular vein to reduce the mean arterial blood pressure (MABP) to 35–45 mm Hg (ht). After 10 min of ischemia, the withdrawn warmed shed blood was reinfused to restore normotension and animals monitored during 3 h. Rats were decapitated, hippocampi were removed and homogenized and then immunoblotting was applied. Results: Protein expression of aromatase and C/EBP was observed after 10 min, 3 h and 24 h reperfusion period at the same level in both control and damaged tissues. These protein expressions peaked at 1 week and decayed at 2 weeks in damaged hippocampi after global ischemia-hypotension. Immunoblot analysis demonstrated that the highest aromatase and C/EBP expression appeared in the damaged (CAO + jvht) hippocampi after 1 week, and gradually reduced after 2–10 weeks. Conclusion: Our findings indicate aromatase and C/EBP expression result from ischemic as well as chronic neurodegenerative processes. ⁎This work is supported by H.U. project number: 02 02 301 009, approved by the ethical committee (2002/63-5)