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p38 mitogen‐activated protein kinase (p38MAPK) upregulates catalase levels in response to low dose H 2 O 2 treatment through enhancement of mRNA stability
Author(s) -
Sen Prosenjit,
Chakraborty Prabir Kumar,
Raha Sanghamitra
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.06.081
Subject(s) - catalase , downregulation and upregulation , messenger rna , protein kinase a , gene silencing , p38 mitogen activated protein kinases , kinase , microbiology and biotechnology , small interfering rna , phosphorylation , rna interference , chemistry , biology , enzyme , rna , biochemistry , gene
V79 fibroblasts were repetitively stressed through multiple exposures to a low dose (30 μM) H 2 O 2 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 μM) of H 2 O 2 . The rise in catalase mRNA levels induced by low concentration (single and multiple dose) H 2 O 2 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 H 2 O 2 treatment.