Hypoxia induces nitric oxide production in mouse microglia via p38 mitogen-activated protein kinase pathway

Sun Young Park, Heasuk Lee, Jinyoung Hur, Sun Yeou Kim, Hocheol Kim, Jae-Hoon Park, Sanghoon Cha, Sang Soo Kang, Gyeong Jae Cho, Wan Sung Choi, Kyoungho Suk
Brain Research. Molecular Brain Research 2002 October 30, 107 (1): 9-16
In vitro exposure of microglial cells to hypoxia induces cellular activation. Also, in vivo studies of glial activation following ischemic hypoxia have shown that neuronal cell death is followed by microglial activation. Thus, it is likely that toxic inflammatory mediators produced by activated microglial cells under hypoxic conditions may exacerbate neuronal injury following cerebral ischemia. Nitric oxide (NO), which is known to be produced by activated microglia, may participate in this process. In the current work, we sought to determine whether and how the production of NO and the expression of inducible NO synthase (iNOS) are triggered by hypoxia in microglial cells. Exposure of established microglial cell lines as well as primary mouse microglial cultures to mild hypoxia (8 h) followed by reoxygenation (24 h) induced the production of NO and TNFalpha, indicating that hypoxia could lead to the inflammatory activation of microglia. Hypoxic induction of NO was accompanied by iNOS induction. Moreover, hypoxia induced the activation of p38 MAPK, but not ERK or JNK/SAPK, in BV-2 mouse microglial cells. SB203580, a specific inhibitor of p38 MAPK, blocked the hypoxic induction of NO and iNOS. Taken together, our results indicated that hypoxia could induce inflammatory activation of microglia, and the hypoxic induction of NO production in microglia is mediated through p38 MAPK pathway. Thus, during cerebral ischemia, hypoxia may not only directly damage neurons, but may also promote neuronal injury indirectly via microglial activation.

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"