Activation of PKC‐ε and ERK1/2 participates in shear‐induced endothelial MCP‐1 expression that is repressed by nitric oxide

Wang, Danny L.; Lien, Sheng-Chieh; Cheng, Jing-Jy; Chao, Yuen-Jen; Hsieh, Hsun-Ping

doi:10.1002/jcp.10259

Cited by 37 publications

(30 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast to ERK5, many of the genes up-regulated in response to ERK1/2 in these cells were observed previously in other systems, including FOS (42), HAS2 (43), PTHLH (44), BIRC3/AIP1 (45), CCL2/MCP1 (46,47), CXCL1 (48), CXCL2 (49), IL-6 (50), IL-8 (51), PTGS2 (52), and IL1B (53). No genes were found to be repressed by ERK1/2 signaling in RPE cells.…”

Section: Characterization Of Map Kinase Signaling In Rpe Cells-mi-supporting

confidence: 63%

Global Gene Expression Analysis of ERK5 and ERK1/2 Signaling Reveals a Role for HIF-1 in ERK5-mediated Responses

Schweppe

Cheung

Ahn

2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

ERK5 is a recently characterized MAPK, which is most similar to the well studied ERK1/2 subfamily but uses distinct mechanisms to elicit responses. To understand the specificity of signaling through ERK5 versus ERK1/2, we examined global gene expression changes in response to each pathway. Microarray measurements in retinal pigment epithelial cells revealed 36 genes regulated by ERK5, all which were novel targets for this pathway. 39 genes were regulated by ERK1/2, which included 11 known genes. Of these genes, 19 were regulated by both pathways. Inspection of the 17 genes uniquely regulated by ERK5 revealed that 14 genes (82%) were previously associated with hypoxia via regulation by HIF-1. In contrast, 16 genes (84%) regulated by either ERK5 or ERK1/2 were implicated in hypoxia, most through mechanisms independent of HIF-1. Of the 20 genes regulated by ERK1/2, only 9 were implicated in hypoxia and were not well characterized hypoxia targets. Thus, unlike ERK5, a mechanistic link between ERK1/2 and HIF-1/HRE could not be established on the basis of gene regulation. Activation of both pathways enhanced transcription from a hypoxiaresponse element and increased HIF-1␣ protein expression. In contrast, ERK5 but not ERK1/2 elevated transcription through GAL4-HIF-1. Most interestingly, ERK5 is not significantly activated by hypoxia in retinal pigment epithelial cells, indicating that ERK5 regulation of these genes is relevant in normoxia rather than hypoxia. Thus, ERK5 and ERK1/2 differ in their mechanisms of gene regulation, and indicate that ERK5 may control hypoxia-responsive genes by a mechanism independent of HIF-1␣ expression control.

show abstract

Section: Characterization Of Map Kinase Signaling In Rpe Cells-mi-supporting

confidence: 63%

Global Gene Expression Analysis of ERK5 and ERK1/2 Signaling Reveals a Role for HIF-1 in ERK5-mediated Responses

Schweppe

Cheung

Ahn

2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…This observation corresponds with the findings that shear stress induced phosphorylation of ERK1/2 was not attenuated by either NOS inhibition (Milkiewicz et al, 2006) or COX2 inhibition (current study). While the present analysis did not identify an upstream pathway leading to ERK1/2 phosphorylation, previous reports indicate that integrin β1 contributes to shear stress activation of ERK1/2 (Ishida et al, 1996) via FAK, Src and PKCε activation (Jalali et al, 1998;Ni et al, 2003).…”

Section: Discussioncontrasting

confidence: 85%

Shear stress‐induced Ets‐1 modulates protease inhibitor expression in microvascular endothelial cells

Milkiewicz

Uchida

Gee

et al. 2008

Journal Cellular Physiology

View full text Add to dashboard Cite

Elevated shear stress within the skeletal muscle microvasculature is implicated in the induction of a longitudinal splitting form of angiogenesis, which is characterized by the lack of basement membrane breakage. We investigated whether the transcriptional regulator, Ets-1, is responsive to changes in hemodynamic forces and if so, whether Ets-1 controls microvascular endothelial cell integrity by inducing the expression of inhibitors of matrix degrading proteases. Rats were treated with prazosin for 2, 4 and 7 days to increase in microvascular shear stress in hindlimb skeletal muscles. In complimentary in vitro experiments, rat microvascular skeletal muscle endothelial cells were exposed to laminar shear stress (15 dyne/cm 2 ) for 0.5, 2, and 24 hours. TaqMan PCR analysis of laser microdissected capillaries isolated from EDL muscles demonstrated transient (after 2 days) induction of Ets-1 gene expression. In cultured cells, a transient up-regulation of Ets-1 mRNA was observed after 2hr shear stimulation, accompanied by increased phosphorylation of Ets-1 and enhanced Ets-1 DNA binding activity. This response was modulated by ERK1/2 and p38 MAP kinases, but was not dependent on NOS or COX-2 activity. PAI-1, TIMP-1 and TIMP-3 mRNA were elevated significantly in prazosin treated EDL, and in response to shear stimulation in vitro. In cultured endothelial cells, Ets-1 RNA interference abolished the shear-induced increases in Ets-1, PAI-1, TIMP-1 and TIMP-3 mRNA expression. These results suggest that enhanced laminar shear stress may act to preserve the integrity of microvascular walls in part through Ets-1-dependent induction of protease inhibitors.

show abstract

“…Shear stress has been shown to stimulate endothelial nitric oxide synthase activity (38,39) and eNOS expression (40). Our recent studies have also demonstrated that endothelial NO plays an important role in attenuating the redox-sensitive responses (5,41,42). Shear stress to ECs also increases the expression of antioxidant enzymes such as Cu/Zn superoxide dismutase and heme oxygenase-1 (43).…”

Section: Discussionmentioning

confidence: 97%

Shear Flow Attenuates Serum-induced STAT3 Activation in Endothelial Cells

Hsieh

Chao

Wang

2003

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

ERK1/2 is involved in shear stress-and cyclic strain-induced early growth response-1 expression (5, 6). We have shown that genes such as monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule (ICAM-1), and c-fos can be induced by hemodynamic forces (7-9). The induction of these genes appears to be a redox-sensitive mechanism because an increased reactive oxygen species is required for this gene induction (7-9). Recent studies indicate that ECs under conditions of shear flow inhibit tumor necrosis factor-and H 2 O 2 -induced responses (10 -12). A recent study (13) has nicely demonstrated an induction of antioxidant response element-mediated genes in ECs exposed to laminar flow. Furthermore, shear flow has been shown to inhibit endothelial proliferation via the induction of growth arrest proteins GADD45 and p21, as well as a decrease in phosphorylation of Rb protein (14). Thus, laminar shear flow appears to play an essential role by protecting ECs from inflammatory responses and endothelial proliferation. However, the detailed mechanisms involved in this shear flowinduced protection remain unclear.Signal transducers and activators of transcriptions (STAT) are a family of functionally related proteins that play key roles in a variety of biological activities. Among these STATs, STAT3 is preferentially activated by interleukin-6 (IL-6) or other related cytokines and is required for gp130-mediated cell-survival signals (15,16). STAT3 has been intensively studied for its role in cell growth, differentiation, apoptosis, transformation, inflammation, and immune response. STAT3 is activated by tyrosine phosphorylation at a single site (Tyr-705) and by serine phosphorylation at 727 (Ser-727). Tyrosine phosphorylation of STAT3 in response to cytokine stimulation is mediated by a Janus kinase, and Src family members have been widely studied (17)(18)(19). Tyrosine phosphorylation is required for STAT3 dimerization, nuclear translocation, and DNA binding. For phosphorylation at Ser-727, there is still controversy in identifying the serine kinases. Activation of kinases, including ERK, JNK, and P38, leading to serine phosphorylation in STAT3 has been documented (16). Ser-727 phosphorylation is involved in STAT3 transcriptional activation. However, there is evidence for a negative role for serine phosphorylation. It has been shown that Ser-727 phosphorylation negatively modulates tyrosine phosphorylation (16,20,21). In addition to this cytokine-induced STAT activation, the receptor protein-tyrosine kinase-mediated activation of STAT remains elusive. Recent studies suggest that STAT3 in ECs can be activated by growth factors such as vascular endothelial growth factor (22), basic fibroblast growth factor (23), granulocyte-macrophase

show abstract

Activation of PKC‐ε and ERK1/2 participates in shear‐induced endothelial MCP‐1 expression that is repressed by nitric oxide

Cited by 37 publications

References 26 publications

Global Gene Expression Analysis of ERK5 and ERK1/2 Signaling Reveals a Role for HIF-1 in ERK5-mediated Responses

Global Gene Expression Analysis of ERK5 and ERK1/2 Signaling Reveals a Role for HIF-1 in ERK5-mediated Responses

Shear stress‐induced Ets‐1 modulates protease inhibitor expression in microvascular endothelial cells

Shear Flow Attenuates Serum-induced STAT3 Activation in Endothelial Cells

Contact Info

Product

Resources

About