The role of mitogen-activated protein kinase phosphatase-1 in oxidative damage-induced cell death

Jun-Ying Zhou, Yusen Liu, Gen Sheng Wu
Cancer Research 2006 May 1, 66 (9): 4888-94
Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a member of the MAPK phosphatase family that functions as a negative regulator of MAPK signaling. MKP-1 is induced by oxidative stress, but the role of its induction in cell death is not fully understood. Here, we show that hydrogen peroxide (H(2)O(2)) induces MKP-1 and activates MAPKs. Induction of MKP-1 by H(2)O(2) correlated with inactivation of p38 and c-Jun-NH(2)-kinase (JNK). Overexpression of MKP-1 increased cell resistance to H(2)O(2)-induced death. Furthermore, we show by small interfering RNA silencing that down-regulation of MKP-1 increases phosphorylated p38 and JNK and subsequent cell death induced by H(2)O(2). More importantly, primary embryonic fibroblasts from mice lacking MKP-1 had a higher level of phosphorylated p38 and JNK and were more sensitive to H(2)O(2)-induced cell death compared with corresponding cells with MKP-1, indicating that p38 and JNK pathways may play important roles in H(2)O(2)-mediated cell death. Thus, these results suggest that activation of MKP-1 is a survival mechanism against oxidative damage.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"