Mediation of BMP7 neuroprotection by MAPK and PKC in rat primary cortical cultures

S. Cox, B. K. Harvey, Joseph F. Sanchez, Jia Yi Wang, Yun Wang

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

We have previously demonstrated that pretreatment with bone morphogenetic protein 7 (BMP7), a trophic factor in the TGFβ superfamily, reduces ischemia-induced brain infarction induced by middle cerebral artery ligation in rats. Since the mitogen-activated protein kinase (MAPK) pathway is involved in many TGFβ-mediated responses, we examined the interaction of BMP7 and MAPK in primary cultures obtained from the cerebral cortex of E16-17 rat embryos. Lactate dehydrogenase (LDH) in the media was used as an index of cell death. BMP7 did not alter LDH levels at low concentration (1.25 nM), but exhibited increased cellular toxicity at higher concentration (>12.5 nM). BMP7 at the low concentration significantly attenuated H2O2-induced increases in LDH activity and decreases in neuronal density. Pharmacological interactions were used to examine if MAPK was involved in this response. BMP7-induced protection was antagonized by the p42,44 MAPK kinase inhibitors PD98059 and U0125. The p38 MAPK antagonist SB203580, and their inactive analog SB202474, also attenuated BMP7-induced protection, suggesting that the interaction with p38 MAPK is nonspecific. Previous studies have indicated that SB202474 has inhibitory effects on other protein kinases. We found that the protein kinase C inhibitor chelerythrine antagonized BMP7-induced protection against H2O2. Western blot analysis indicated that BMP7 increased phosphorylation of p42,44 MAPK and PKC. Taken together, our data suggest that BMP7 is neuroprotective at low concentrations in primary cortical cell culture. The protective effects of BMP7 may involve the activation of p42,44 MAPK and PKC.

Original languageEnglish
Pages (from-to)55-61
Number of pages7
JournalBrain Research
Volume1010
Issue number1-2
DOIs
Publication statusPublished - Jun 4 2004
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein 7
Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
L-Lactate Dehydrogenase
p38 Mitogen-Activated Protein Kinases
Neuroprotection
Brain Infarction
Primary Cell Culture
Protein C Inhibitor
Mitogen-Activated Protein Kinase Kinases
Middle Cerebral Artery
Protein Kinase Inhibitors
Cerebral Cortex
Protein Kinases
Protein Kinase C
Ligation
Cell Death
Ischemia
Embryonic Structures
Western Blotting

Keywords

  • Bone morphogenetic protein 7
  • Development and regeneration
  • Mitogen activated protein kinase
  • Neuroprotection
  • Neurotrophic factors: biological effects
  • Protein kinase C

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mediation of BMP7 neuroprotection by MAPK and PKC in rat primary cortical cultures. / Cox, S.; Harvey, B. K.; Sanchez, Joseph F.; Wang, Jia Yi; Wang, Yun.

In: Brain Research, Vol. 1010, No. 1-2, 04.06.2004, p. 55-61.

Research output: Contribution to journalArticle

Cox, S. ; Harvey, B. K. ; Sanchez, Joseph F. ; Wang, Jia Yi ; Wang, Yun. / Mediation of BMP7 neuroprotection by MAPK and PKC in rat primary cortical cultures. In: Brain Research. 2004 ; Vol. 1010, No. 1-2. pp. 55-61.
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