Overexpression of heme oxygenase in neuronal cells, the possible interaction with Tau.
Increased expression of heme oxygenase-1 (HO-1) is a common feature in a number of neurodegenerative diseases. Interestingly, the spatial distribution of HO-1 expression in diseased brain is essentially identical to that of pathological expression of tau. In this study, we explored the relationship between HO-1 and tau, using neuroblastoma cells stably transfected with sense and antisense HO-1 constructs as well as with the vector alone. In transfected cells overexpressing HO-1, the activity of heme oxygenase was increased, and conversely, the level of tau protein was dramatically decreased when compared with antisense HO-1 or CEP transfected cells. The suppression of tau protein expression was almost completely reversed by zinc-deuteroporphyrin, a specific inhibitor of heme oxygenase activity. The activated forms of ERKs (extracellular signal-regulated kinases) were also decreased in cells overexpressing HO-1 although no changes in the expression of total ERK-1/2 proteins were observed. These data are in agreement with the finding that the expression of tau is regulated through signal cascades including the ERKs, whose activities are modulated by oxidative stresses. The expression of tau and HO-1 may be regulated by oxidative stresses in a coordinated manner and play a pivotal role in the cytoprotection of neuronal cells.
Takeda
A
A
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Perry
G
G
Abraham
N G
NG
Dwyer
B E
BE
Kutty
R K
RK
Laitinen
J T
JT
Petersen
R B
RB
Smith
M A
MA
D000544:Alzheimer Disease / Q000201:enzymology; D015152:Blotting, Northern; D002470:Cell Survival; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009447:Neuroblastoma / Q000201:enzymology; D009474:Neurons / Q000201:enzymology*; D018384:Oxidative Stress; D010957:Plasmids; D011494:Protein Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; D016875:tau Proteins; D006861:Hydrogen Peroxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D011494:Protein Kinases; D048056:Mitogen-Activated Protein Kinase 9; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases