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

研究成果: 雜誌貢獻文章

32 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)55-61
頁數7
期刊Brain Research
1010
發行號1-2
DOIs
出版狀態已發佈 - 六月 4 2004
對外發佈Yes

指紋

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

ASJC Scopus subject areas

  • Neuroscience(all)

引用此文

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.

於: Brain Research, 卷 1010, 編號 1-2, 04.06.2004, p. 55-61.

研究成果: 雜誌貢獻文章

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. 於: Brain Research. 2004 ; 卷 1010, 編號 1-2. 頁 55-61.
@article{57fb62855468466d8d5e12c8cd7d66f1,
title = "Mediation of BMP7 neuroprotection by MAPK and PKC in rat primary cortical cultures",
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.",
keywords = "Bone morphogenetic protein 7, Development and regeneration, Mitogen activated protein kinase, Neuroprotection, Neurotrophic factors: biological effects, Protein kinase C",
author = "S. Cox and Harvey, {B. K.} and Sanchez, {Joseph F.} and Wang, {Jia Yi} and Yun Wang",
year = "2004",
month = "6",
day = "4",
doi = "10.1016/j.brainres.2004.02.068",
language = "English",
volume = "1010",
pages = "55--61",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Mediation of BMP7 neuroprotection by MAPK and PKC in rat primary cortical cultures

AU - Cox, S.

AU - Harvey, B. K.

AU - Sanchez, Joseph F.

AU - Wang, Jia Yi

AU - Wang, Yun

PY - 2004/6/4

Y1 - 2004/6/4

N2 - 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.

AB - 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.

KW - Bone morphogenetic protein 7

KW - Development and regeneration

KW - Mitogen activated protein kinase

KW - Neuroprotection

KW - Neurotrophic factors: biological effects

KW - Protein kinase C

UR - http://www.scopus.com/inward/record.url?scp=2342534498&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2342534498&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2004.02.068

DO - 10.1016/j.brainres.2004.02.068

M3 - Article

C2 - 15126117

AN - SCOPUS:2342534498

VL - 1010

SP - 55

EP - 61

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1-2

ER -