Membrane Depolarization Mediates Phosphorylation and Nuclear Translocation of CREB in Vascular Smooth Muscle Cells

Stevenson, Andrá S.; Cartin, Laura; Wellman, Theresa L.; Dick, Melissa H.; Nelson, Mark T.; Lounsbury, Karen M.

doi:10.1006/excr.2000.5107

Cited by 49 publications

(57 citation statements)

References 36 publications

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“…24 In the present study, we found that specific signal inhibitors, PD98059 and U0126 for ERK1/2, SB203580 and SB202190 for P38-MAPK, and LY294002 and wortmannin for PI3K/Akt, markedly decreased AGEsinduced upregulation of K Ca 3.1 channel expression in rat VSMCs, indicating that activation of these cellular signaling pathways mediate the AGEs-induced increase of K Ca 3.1 channels. This is supported by previous reports, in which ERK induces an increase of proliferative gene expression, eg, the AP-1 family member c-fos, [25][26][27] and the increased production of c-fos leads to induction of K Ca 3.1 expression through AP-1 promoter elements. 28 In addition to the upregulation of K Ca 3.1 current and K Ca 3.1 expression by AGEs, the recent studies reported that K Ca 3.1 channels were activated by PI(3)P, which is produced by PI3K from phosphatidylinositol.…”

Section: Discussionsupporting

confidence: 89%

KCa3.1 channels mediate the increase of cell migration and proliferation by advanced glycation endproducts in cultured rat vascular smooth muscle cells

Zhao

Wang

et al. 2013

Laboratory Investigation

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The mechanisms underlying the involvement of advanced glycation endproducts (AGEs) in diabetic atherosclerosis are not fully understood. The present study was designed to investigate whether intermediate-conductance Ca 2 þ -activated K þ channels (K Ca 3.1 channels) are involved in migration and proliferation induced by AGEs in cultured rat vascular smooth muscle cells (VSMCs) using approaches of whole-cell patch voltage-clamp, cell proliferation and migration assay, and western blot analysis. It was found that the current density and protein level of K Ca 3.1 channels were enhanced in cells incubated with AGE-BSA (bovine serum albumin), and the effects were reversed by co-incubation of AGE-BSA with anti-RAGE (anti-receptors of AGEs) antibody. The ERK1/2 inhibitors PD98059 and U0126, the P38-MAPK inhibitors SB203580 and SB202190, or the PI3K inhibitors LY294002 and wortmannin countered the K Ca 3.1 channel expression by AGE-BSA. In addition, AGE-BAS increased cell migration and proliferation, and the effects were fully reversed with anti-RAGE antibody, the K Ca 3.1 channel blocker TRAM-34, or K Ca 3.1 small interfering RNA. These results demonstrate for the first time that AGEs-induced increase of migration and proliferation is related to the upregulation of K Ca 3.1 channels in rat VMSCs, and the intracellular signals ERK1/2, P38-MAPK and PI3K are involved in the regulation of K Ca 3.1 channel expression.

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Section: Discussionsupporting

confidence: 89%

KCa3.1 channels mediate the increase of cell migration and proliferation by advanced glycation endproducts in cultured rat vascular smooth muscle cells

Zhao

Wang

et al. 2013

Laboratory Investigation

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“…It has been demonstrated previously that CREB phosphorylation results in its cytosolic to nuclear translocation in VSMC (35). To determine whether iPLA 2 ␤ participates in CREB nuclear localization by affecting CREB phosphorylation, we examined effects of Ang II on the subcellular distribution of phospho-CREB (p-CREB) in VSMC from WT and iPLA 2 ␤-null mice.…”

Section: Volume 286 • Number 52 • December 30 2011mentioning

confidence: 99%

Identification of a cAMP-response Element in the Regulator of G-protein Signaling-2 (RGS2) Promoter as a Key Cis-regulatory Element for RGS2 Transcriptional Regulation by Angiotensin II in Cultured Vascular Smooth Muscles

Xie

Liu

et al. 2011

Journal of Biological Chemistry

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Background: Angiotensin II-induced regulator of G-protein signaling-2 (RGS2) expression is an important negative feedback loop in blood pressure homeostasis. Results: A conserved cAMP-response element-binding protein (CREB) binding site is found in the RGS2 promoter and is associated with three SNPs identified in hypertensive patients. Conclusion: CREB links the angiotensin II/PKC/iPLA 2 ␤/PKA signaling and RGS2 transcription. Significance: This study delineates a negative feedback loop with potential importance in the pathogenesis of human hypertension.

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“…Although its etiology remains unclear, elevated levels of circulating mitogens, dysfunction or down-regulation of receptors and ion channels, upregulation of transporters, and heightened activity of elastases and glycoproteins have been implicated in IPAH (5,6,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) Transient receptor potential (TRP) channel genes may encode subunits that form receptor-(ROC) and store-(SOC) operated Ca 2ϩ channels in many cell types, including PASMC and pulmonary artery endothelial cells (PAEC) (28,(30)(31)(32)(33)(34). Ca 2ϩ entry through ROC and SOC increases [Ca 2ϩ ] cyt , allowing for phosphorylation of signal transduction proteins and transcription factors (23,24,(35)(36)(37)(38), that are essential for the progression of the cell cycle (21). High levels of [Ca 2ϩ ] cyt and sufficient levels of Ca 2ϩ in the SR are required for vascular smooth muscle cell proliferation (22,25,39).…”

mentioning

confidence: 99%

“…Ca 2ϩ entry through ROC and SOC increases [Ca 2ϩ ] cyt , allowing for phosphorylation of signal transduction proteins and transcription factors (23,24,(35)(36)(37)(38), that are essential for the progression of the cell cycle (21). High levels of [Ca 2ϩ ] cyt and sufficient levels of Ca 2ϩ in the SR are required for vascular smooth muscle cell proliferation (22,25,39).…”

mentioning

confidence: 99%

Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension

Fantozzi

Remillard

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

395

366

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Pulmonary vascular medial hypertrophy caused by excessive pulmonary artery smooth muscle cell (PASMC) proliferation is a major cause for the elevated pulmonary vascular resistance in patients with idiopathic pulmonary arterial hypertension (IPAH). Increased Ca 2؉ influx is an important stimulus for PASMC proliferation. Transient receptor potential (TRP) channel genes encode Ca 2؉ channels that are responsible for Ca 2؉ entry during cell proliferation. Normal human PASMC expressed multiple canonical TRP (TRPC) isoforms; TRPC6 was highly expressed and TRPC3 was minimally expressed. The protein expression of TRPC6 in normal PASMC closely correlated with the expression of Ki67, suggesting that TRPC6 expression is involved in the transition of PASMC from quiescent phase to mitosis. In lung tissues and PASMC from IPAH patients, the mRNA and protein expression of TRPC3 and -6 were much higher than in those from normotensive or secondary pulmonary hypertension patients. Inhibition of TRPC6 expression with TRPC6 small interfering RNA markedly attenuated IPAH-PASMC proliferation. These results demonstrate that expression of TRPC channels correlates with the progression of the cell cycle in PASMC. TRPC channel overexpression may be partially responsible for the increased PASMC proliferation and pulmonary vascular medial hypertrophy in IPAH patients.I diopathic pulmonary arterial hypertension (IPAH) is a fatal disease that causes right heart failure and death. The elevated pulmonary vascular resistance (PVR) and arterial pressure in IPAH patients result mainly from pulmonary vasoconstriction, vascular remodeling, and in situ thrombosis (1). A central aspect of pulmonary vascular remodeling is medial hypertrophy caused by sustained pulmonary vasoconstriction (2-4), excessive pulmonary artery smooth muscle cell (PASMC) proliferation (5), and inhibited PASMC apoptosis (6, 7), resulting in a narrowed vascular lumen and increased PVR. Although its etiology remains unclear, elevated levels of circulating mitogens, dysfunction or down-regulation of receptors and ion channels, upregulation of transporters, and heightened activity of elastases and glycoproteins have been implicated in IPAH (5,6,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) Transient receptor potential (TRP) channel genes may encode subunits that form receptor-(ROC) and store-(SOC) operated Ca 2ϩ channels in many cell types, including PASMC and pulmonary artery endothelial cells (PAEC) (28,(30)(31)(32)(33)(34). Ca 2ϩ entry through ROC and SOC increases [Ca 2ϩ ] cyt , allowing for phosphorylation of signal transduction proteins and transcription factors (23,24,(35)(36)(37)(38), that are essential for the progression of the cell cycle (21). High levels of [Ca 2ϩ ] cyt and sufficient levels of Ca 2ϩ in the SR are required for vascular smooth muscle cell proliferation (22,25,39). Because they regulate SR and cytoplasmic Ca 2ϩ , CCE and SOC may play significant roles in regulating cell proliferation (28,29). This study tested the hypothesis that canonical TRP (TRPC...

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Membrane Depolarization Mediates Phosphorylation and Nuclear Translocation of CREB in Vascular Smooth Muscle Cells

Cited by 49 publications

References 36 publications

KCa3.1 channels mediate the increase of cell migration and proliferation by advanced glycation endproducts in cultured rat vascular smooth muscle cells

KCa3.1 channels mediate the increase of cell migration and proliferation by advanced glycation endproducts in cultured rat vascular smooth muscle cells

Identification of a cAMP-response Element in the Regulator of G-protein Signaling-2 (RGS2) Promoter as a Key Cis-regulatory Element for RGS2 Transcriptional Regulation by Angiotensin II in Cultured Vascular Smooth Muscles

Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension

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