p38 mitogen-activated protein kinase (p38MAPK) upregulates catalase levels in response to low dose H2O2 treatment through enhancement of mRNA stability.
V79 fibroblasts were repetitively stressed through multiple exposures to a low dose (30 microM) H2O2 in culture for 4 weeks. Catalase activity, protein levels and mRNA levels increased markedly (5-6-fold) during this time and these augmentations were inhibited by the simultaneous presence of SB203580, an inhibitor of p38 mitogen-activated protein kinase (p38MAPK). p38MAPK became dually phosphorylated and ATF-2, a p38MAPK substrate also became increasingly phosphorylated over the repetitive stress period. Short interfering RNA that induced effective silencing of p38MAPK, was used to silence p38MAPK in V79 fibroblasts. Silencing of p38MAPK drastically hindered the elevation in catalase (protein and mRNA) levels observed after a single low dose (50 microM) of H2O. The rise in catalase mRNA levels induced by low concentration (single and multiple dose) H2O2 treatment was established to be unconnected with transcriptional upregulation but was brought forth primarily by an enhancement in catalase mRNA stability through the action of p38MAPK. Therefore, our data strongly indicate that activation of p38MAPK is a key controlling step in the upregulation of catalase levels by low dose H2O2 treatment.
Sen
Prosenjit
P
Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064, India.
Chakraborty
Prabir Kumar
PK
Raha
Sanghamitra
S
D051698:Activating Transcription Factor 2; D000818:Animals; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D006224:Cricetinae; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D020868:Gene Silencing; D006861:Hydrogen Peroxide / Q000633:toxicity; D007093:Imidazoles / Q000494:pharmacology; D018384:Oxidative Stress; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D002374:Catalase; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580