1. Catalog
  2. Citations
  3. PubMed:22954673

PubMed: 22954673

Title
Heme modulates smooth muscle cell proliferation and migration via NADPH oxidase: a counter-regulatory role for heme oxygenase system.
Journal
Atherosclerosis
Volume
224
Issue
None
Pages
394-400
Date
2012-10-01
Authors
Arruda MA | Assreuy J | Barcellos-de-Souza P | Barja-Fidalgo C | Moraes JA | Nascimento-Silva V | Rodrigues G | Silva SV

Evidence e646300414
JSON

In VSMC pretreated with the ERK-2 inhibitor PD98059 (10 mM), migration induced by heme was partially inhibited (Fig. 3A) and heme proliferative effect on VSMC was impaired (Fig. 3B).

a(CHEBI:"2-(2-amino-3-methoxyphenyl)chromen-4-one") decreases bp(GO:"cell proliferation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

a(CHEBI:"2-(2-amino-3-methoxyphenyl)chromen-4-one") decreases bp(GO:"cell migration") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

Evidence 362663cc2c
JSON

Fig. 4 shows that the inhibition of HO activity by both, SnPP (Fig. 4A) or ZnPP (Fig. 4B), potentiates the effect of heme on VSMC proliferation.

a(CHEBI:"zinc protoporphyrin") decreases act(p(RGD:Hmox1)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

complex(a(CHEBI:"tin atom"), a(CHEBI:protoporphyrin)) decreases act(p(RGD:Hmox1)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

Evidence 3a4df2086e
JSON

Additionally, it was observed that inhibition of HO-1 by ZnPP induced a further increase in hemeinduced ROS production (Fig. 4C), suggesting that activation of HO system attenuates the NADPHox-dependent activation of VSMC induced by heme.

a(CHEBI:"zinc protoporphyrin") decreases act(p(RGD:Hmox1)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

p(RGD:Hmox1) decreases a(MESH:"Reactive Oxygen Species") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

Evidence f17f6800d5
JSON

Heme effects were shown to be redoxsensitive, since the antioxidant Trolox (100 mM) abrogated heme-induced VSMC migration and proliferation (Fig. 1C,D).

a(CHEBI:Trolox) decreases bp(GO:"cell proliferation") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Muscle, Smooth, Vascular
Text Location
Results

a(CHEBI:Trolox) decreases bp(GO:"cell migration") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Muscle, Smooth, Vascular
Text Location
Results

Evidence 36314d26b6
JSON

Corroborating recent studies that showed heme as an inductor of ROS generation via NADPHox in neutrophils, macrophages and in VSMC [7,8,19], the pretreatment of cells with DPI (10 mM), a NADPHox inhibitor [20], prevented heme-induced ROS production in A7r5 VSMC (Fig. 2A).

a(CHEBI:dibenziodolium) decreases a(MESH:"Reactive Oxygen Species") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

a(CHEBI:heme) increases a(MESH:"Reactive Oxygen Species") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

Evidence 35ce005125
JSON

Moreover, DPI strongly inhibited heme-induced VSMC migration (Fig. 2B) and blunted the proliferative capability of heme-treated VSMC that reached levels below the controls. (Fig. 2C), indicating that heme effects on VSMC migration and proliferation are modulated by NADPHox.

a(CHEBI:dibenziodolium) decreases bp(GO:"cell proliferation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

a(CHEBI:dibenziodolium) decreases bp(GO:"cell migration") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

Evidence 9736722e3d
JSON

As can be observed in Fig. 1, heme has a potent chemotactic activity on VSMC (Fig. 1A), and is also a potent inducer of VSMC proliferation (Fig. 1B).

a(CHEBI:heme) increases bp(GO:"cell proliferation") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Muscle, Smooth, Vascular
Text Location
Results

Evidence ddaac3fece
JSON

Accordingly, Fig. 2A shows that heme (10 mM) induces a strong ROS production after 1 h of incubation with VSMC.

a(CHEBI:heme) increases a(MESH:"Reactive Oxygen Species") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Muscle, Smooth, Vascular
Text Location
Results

Evidence bbb4ab796f
JSON

On the other hand, heme induced HO-1 expression in VSMC (Suppl. Fig. 2).

a(CHEBI:heme) increases p(RGD:Hmox1) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

Evidence 7635a01249
JSON

Among the redox-sensitive molecules, ERK-2, a member of MAPK family, is of crucial importance to VSMC proliferation and migration [21].

bp(GO:"cell migration") positiveCorrelation p(RGD:Mapk1) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

bp(GO:"cell proliferation") positiveCorrelation p(RGD:Mapk1) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

p(RGD:Mapk1) positiveCorrelation bp(GO:"cell proliferation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

p(RGD:Mapk1) positiveCorrelation bp(GO:"cell migration") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Muscle, Smooth, Vascular
Text Location
Results

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.