Changes in expression of p38 mitogen-activated protein kinase in the dorsal motor nucleus of the vagus nerve and hypoglossal nucleus after axotomy in adult rats.
Mitogen-activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli. P38 MAP kinase is one of the MAP kinase family and is activated by proinflammatory cytokines and environmental stresses. Activating transcription factor-2 (ATF-2) is one of the targets for p38 MAP kinase. To obtain information on the role of the p38 MAP kinase in the neurons and glial cells after axotomy, we investigated changes of expression of p38 MAP kinase, MAP kinase kinase (MKK) 3, MKK4, MKK6 and ATF-2 in the dorsal motor nucleus of the vagus nerve and the hypoglossal nucleus following axotomy in rats using in situ hybridization and immunohistochemical techniques. Expression of p38 MAP kinase mRNA was observed in the neurons in control rats and showed no remarkable changes after axotomy in both nuclei. On the other hand, expression of p38 MAP kinase mRNA was observed in the perineuronal microglias after axotomy. The expression of p38 MAP kinase, activated p38 MAP kinase, MKK3 and ATF-2 were immunohistochemically observed in neurons of control rats in both nuclei. After axotomy, the expression of p38 MAP kinase, active and inactive, and ATF-2 in neurons were reduced in both nuclei, while expression of mRNA of p38 MAP kinase showed no reduction in neurons. These findings indicate that p38 MAP kinase is functionally regulated not by synthesis but by phosphorylation and regulates the activation of ATF-2 in neurons, and this cascade plays some role in retrograde neuronal reactions. Moreover, perineuronal microglial cells showed strong expression of p38 MAP kinase, active and inactive, after axotomy in both nuclei. These findings suggest that p38 MAP kinase is related to microglial cell reactions after axotomy.
Shimokawara
Tatsuo
T
Department of Pathology, Nara Medical University, Kashihara, Japan.
Yamada
Eiji
E
Masui
Katsuya
K
Mishima
Kenji
K
Enomoto
Yasunori
Y
Inoue
Kazuya
K
Sakaki
Toshisuke
T
Ichijima
Kunio
K
D051698:Activating Transcription Factor 2; D000818:Animals; D019771:Axotomy; D001933:Brain Stem / Q000201:enzymology / Q000473:pathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis; D004789:Enzyme Activation; D007002:Hypoglossal Nerve / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; D017628:Microglia / Q000201:enzymology / Q000473:pathology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000096:biosynthesis; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis*; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000096:biosynthesis; D014630:Vagus Nerve / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
D051698:Activating Transcription Factor 2; C497107:Atf2 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; D020929:Mitogen-Activated Protein Kinase Kinases