Transient signaling of Erk1/2, Akt and PLCγ induced by nerve growth factor in brain capillary endothelial cells

Shimon Lecht; Hadar Arien-Zakay; Yoav Wagenstein; Seiji Inoue; Cezary Marcinkiewicz; Peter I. Lelkes; Philip Lazarovici

doi:10.1016/j.vph.2010.04.005

Transient signaling of Erk1/2, Akt and PLCγ induced by nerve growth factor in brain capillary endothelial cells

Shimon Lecht, Hadar Arien-Zakay, Yoav Wagenstein, Seiji Inoue, Cezary Marcinkiewicz, Peter I. Lelkes, Philip Lazarovici^*

^*Corresponding author for this work

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Cumulative evidences suggest that nerve growth factor (NGF) promotes angiogenic effects such as proliferation and migration of endothelial cells (ECs) from different vascular beds, induces capillary sprouting in chorioallantoic membrane and improves in vivo vascularization in a hind-limb ischemic model. In the present study, we sought to investigate the signaling properties of NGF in a microcapillary ECs model compared to those of a neuronal model. NGF-induced phosphorylation of signaling molecules Erk1/2, Akt and PLCγ were measured using Western blotting and compared between mouse NGF (mNGF) and snake venom NGF analogues. NGFs-induced signaling was TrkA mediated as evident by inhibition with the TrkA antagonist K252a. NGF and its analogues-induced signaling in ECs were characterized by a transient effect in contrast to a prolonged stimulation in neuronal cells. The potency of mouse, cobra and viper NGFs to induce Erk1/2 phosphorylation in ECs was higher than in neurons. In ECs, mNGF exhibited the highest efficacy of stimulation of Erk1/2 phosphorylation, followed by viper and cobra NGFs. The efficacy of stimulation of Erk1/2 phosphorylation measured with neurons was opposite from that in ECs. NGF-induced temporal signaling differences between ECs and neurons may explain the dual vascular and neurotrophic effects of this growth factor.

Original language	English
Pages (from-to)	107-114
Number of pages	8
Journal	Vascular Pharmacology
Volume	53
Issue number	3-4
DOIs	https://doi.org/10.1016/j.vph.2010.04.005
State	Published - Sep 2010

Bibliographical note

Funding Information:
This work was supported in part by a grant-in-aid form the Stein Family Foundation (PL and PIL); PL is affiliated and partially supported by the David R. Bloom Center for Pharmacy ; and the Dr. Adolf and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics at The Hebrew University of Jerusalem, Israel ; SL is supported by “Eshkol” fellowship from the Israeli Ministry of Science and Technology , and acknowledge the travel support from Boehringer Ingelhein Fonds. The authors would like to acknowledge Ms. Dana Stoler for technical assistance, Ms. Zehava Cohen for graphics design and the constructive remarks of the reviewers.

Keywords

Angiogenesis
Endothelium
Erk1/2-Akt-PLCγ
NGF
Signaling

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.vph.2010.04.005

Cite this

@article{b5b60931fd884aea91337dacf8a3d244,

title = "Transient signaling of Erk1/2, Akt and PLCγ induced by nerve growth factor in brain capillary endothelial cells",

abstract = "Cumulative evidences suggest that nerve growth factor (NGF) promotes angiogenic effects such as proliferation and migration of endothelial cells (ECs) from different vascular beds, induces capillary sprouting in chorioallantoic membrane and improves in vivo vascularization in a hind-limb ischemic model. In the present study, we sought to investigate the signaling properties of NGF in a microcapillary ECs model compared to those of a neuronal model. NGF-induced phosphorylation of signaling molecules Erk1/2, Akt and PLCγ were measured using Western blotting and compared between mouse NGF (mNGF) and snake venom NGF analogues. NGFs-induced signaling was TrkA mediated as evident by inhibition with the TrkA antagonist K252a. NGF and its analogues-induced signaling in ECs were characterized by a transient effect in contrast to a prolonged stimulation in neuronal cells. The potency of mouse, cobra and viper NGFs to induce Erk1/2 phosphorylation in ECs was higher than in neurons. In ECs, mNGF exhibited the highest efficacy of stimulation of Erk1/2 phosphorylation, followed by viper and cobra NGFs. The efficacy of stimulation of Erk1/2 phosphorylation measured with neurons was opposite from that in ECs. NGF-induced temporal signaling differences between ECs and neurons may explain the dual vascular and neurotrophic effects of this growth factor.",

keywords = "Angiogenesis, Endothelium, Erk1/2-Akt-PLCγ, NGF, Signaling",

author = "Shimon Lecht and Hadar Arien-Zakay and Yoav Wagenstein and Seiji Inoue and Cezary Marcinkiewicz and Lelkes, {Peter I.} and Philip Lazarovici",

note = "Funding Information: This work was supported in part by a grant-in-aid form the Stein Family Foundation (PL and PIL); PL is affiliated and partially supported by the David R. Bloom Center for Pharmacy ; and the Dr. Adolf and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics at The Hebrew University of Jerusalem, Israel ; SL is supported by “Eshkol” fellowship from the Israeli Ministry of Science and Technology , and acknowledge the travel support from Boehringer Ingelhein Fonds. The authors would like to acknowledge Ms. Dana Stoler for technical assistance, Ms. Zehava Cohen for graphics design and the constructive remarks of the reviewers.",

year = "2010",

month = sep,

doi = "10.1016/j.vph.2010.04.005",

language = "אנגלית",

volume = "53",

pages = "107--114",

journal = "Vascular Pharmacology",

issn = "1537-1891",

publisher = "Elsevier Inc.",

number = "3-4",

}

TY - JOUR

T1 - Transient signaling of Erk1/2, Akt and PLCγ induced by nerve growth factor in brain capillary endothelial cells

AU - Lecht, Shimon

AU - Arien-Zakay, Hadar

AU - Wagenstein, Yoav

AU - Inoue, Seiji

AU - Marcinkiewicz, Cezary

AU - Lelkes, Peter I.

AU - Lazarovici, Philip

N1 - Funding Information: This work was supported in part by a grant-in-aid form the Stein Family Foundation (PL and PIL); PL is affiliated and partially supported by the David R. Bloom Center for Pharmacy ; and the Dr. Adolf and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics at The Hebrew University of Jerusalem, Israel ; SL is supported by “Eshkol” fellowship from the Israeli Ministry of Science and Technology , and acknowledge the travel support from Boehringer Ingelhein Fonds. The authors would like to acknowledge Ms. Dana Stoler for technical assistance, Ms. Zehava Cohen for graphics design and the constructive remarks of the reviewers.

PY - 2010/9

Y1 - 2010/9

N2 - Cumulative evidences suggest that nerve growth factor (NGF) promotes angiogenic effects such as proliferation and migration of endothelial cells (ECs) from different vascular beds, induces capillary sprouting in chorioallantoic membrane and improves in vivo vascularization in a hind-limb ischemic model. In the present study, we sought to investigate the signaling properties of NGF in a microcapillary ECs model compared to those of a neuronal model. NGF-induced phosphorylation of signaling molecules Erk1/2, Akt and PLCγ were measured using Western blotting and compared between mouse NGF (mNGF) and snake venom NGF analogues. NGFs-induced signaling was TrkA mediated as evident by inhibition with the TrkA antagonist K252a. NGF and its analogues-induced signaling in ECs were characterized by a transient effect in contrast to a prolonged stimulation in neuronal cells. The potency of mouse, cobra and viper NGFs to induce Erk1/2 phosphorylation in ECs was higher than in neurons. In ECs, mNGF exhibited the highest efficacy of stimulation of Erk1/2 phosphorylation, followed by viper and cobra NGFs. The efficacy of stimulation of Erk1/2 phosphorylation measured with neurons was opposite from that in ECs. NGF-induced temporal signaling differences between ECs and neurons may explain the dual vascular and neurotrophic effects of this growth factor.

AB - Cumulative evidences suggest that nerve growth factor (NGF) promotes angiogenic effects such as proliferation and migration of endothelial cells (ECs) from different vascular beds, induces capillary sprouting in chorioallantoic membrane and improves in vivo vascularization in a hind-limb ischemic model. In the present study, we sought to investigate the signaling properties of NGF in a microcapillary ECs model compared to those of a neuronal model. NGF-induced phosphorylation of signaling molecules Erk1/2, Akt and PLCγ were measured using Western blotting and compared between mouse NGF (mNGF) and snake venom NGF analogues. NGFs-induced signaling was TrkA mediated as evident by inhibition with the TrkA antagonist K252a. NGF and its analogues-induced signaling in ECs were characterized by a transient effect in contrast to a prolonged stimulation in neuronal cells. The potency of mouse, cobra and viper NGFs to induce Erk1/2 phosphorylation in ECs was higher than in neurons. In ECs, mNGF exhibited the highest efficacy of stimulation of Erk1/2 phosphorylation, followed by viper and cobra NGFs. The efficacy of stimulation of Erk1/2 phosphorylation measured with neurons was opposite from that in ECs. NGF-induced temporal signaling differences between ECs and neurons may explain the dual vascular and neurotrophic effects of this growth factor.

KW - Angiogenesis

KW - Endothelium

KW - Erk1/2-Akt-PLCγ

KW - NGF

KW - Signaling

UR - http://www.scopus.com/inward/record.url?scp=77956181361&partnerID=8YFLogxK

U2 - 10.1016/j.vph.2010.04.005

DO - 10.1016/j.vph.2010.04.005

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 20434587

AN - SCOPUS:77956181361

SN - 1537-1891

VL - 53

SP - 107

EP - 114

JO - Vascular Pharmacology

JF - Vascular Pharmacology

IS - 3-4

ER -

Transient signaling of Erk1/2, Akt and PLCγ induced by nerve growth factor in brain capillary endothelial cells

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this