TY - JOUR
T1 - Endoplasmic reticulum stress is accompanied by activation of NF-κB in amyotrophic lateral sclerosis
AU - Prell, T.
AU - Lautenschläger, J.
AU - Weidemann, L.
AU - Ruhmer, J.
AU - Witte, O. W.
AU - Grosskreutz, J.
N1 - Funding Information:
This research is supported by a BMBF (the Bundesministerium fürBildung und Forschung) grant PYRAMID to JG in the framework of the ERANET E-RARE program ( http://www.e-rare.eu ) and was undertaken in cooperation with the BMBF funded MND-NET. TP is supported by an IZKF grant from University Hospital Jena. For technical assistance we thank Svetlana Tausch, Julia Oberland and Diana Freitag. We thank Alexandra Kretz for supplying the NF-κB antibody.
PY - 2014
Y1 - 2014
N2 - Background: Recent studies have indicated that endoplasmic reticulum (ER) stress is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). ER stress occurs when the ER-mitochondria calcium cycle is disturbed and misfolded proteins accumulate in the ER. To cope with ER stress, cells activate the unfolded protein response (UPR). Accumulating evidence from non-neuronal cell models suggests that there is extensive cross-talk between the UPR and the NF-κB pathway. Methods: Here we investigated the expression of NF-κB and the main UPR markers X-box binding protein 1 (XBP1), basic leucine-zipper transcription factor 6 (ATF6) and phosphorylated eukaryotic initiation factor-2α (p-eIF2) in mutated SOD1G93A cell models of ALS, as well as their modulation by lipopolysaccharide and ER-stressing (tunicamycin) stimuli. Results: Expression of NF-κB was enhanced in the presence of SOD1G93A. Lipopolysaccharide did not induce the UPR in NSC34 cells and motor neurons in a mixed motor neuron-glia coculture system. The induction of the UPR by tunicamycin was accompanied by activation of NF-κB in NSC34 cells and motor neurons. Conclusion: Our data linked two important pathogenic mechanisms of ALS, ER stress and NF-κB signalling, in motor neurons.
AB - Background: Recent studies have indicated that endoplasmic reticulum (ER) stress is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). ER stress occurs when the ER-mitochondria calcium cycle is disturbed and misfolded proteins accumulate in the ER. To cope with ER stress, cells activate the unfolded protein response (UPR). Accumulating evidence from non-neuronal cell models suggests that there is extensive cross-talk between the UPR and the NF-κB pathway. Methods: Here we investigated the expression of NF-κB and the main UPR markers X-box binding protein 1 (XBP1), basic leucine-zipper transcription factor 6 (ATF6) and phosphorylated eukaryotic initiation factor-2α (p-eIF2) in mutated SOD1G93A cell models of ALS, as well as their modulation by lipopolysaccharide and ER-stressing (tunicamycin) stimuli. Results: Expression of NF-κB was enhanced in the presence of SOD1G93A. Lipopolysaccharide did not induce the UPR in NSC34 cells and motor neurons in a mixed motor neuron-glia coculture system. The induction of the UPR by tunicamycin was accompanied by activation of NF-κB in NSC34 cells and motor neurons. Conclusion: Our data linked two important pathogenic mechanisms of ALS, ER stress and NF-κB signalling, in motor neurons.
UR - http://www.scopus.com/inward/record.url?scp=84898773604&partnerID=8YFLogxK
U2 - 10.1016/j.jneuroim.2014.03.005
DO - 10.1016/j.jneuroim.2014.03.005
M3 - Journal articles
C2 - 24666819
AN - SCOPUS:84898773604
SN - 0165-5728
VL - 270
SP - 29
EP - 36
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -
