A Potential Role for Extracellular Signal-regulated Kinases in Prostaglandin F2α-induced Protein Synthesis in Smooth Muscle Cells

Rao, Gadiparthi N.; Madamanchi, Nageswara R.; Lele, Manjiri; Gadiparthi, Laxmisilpa; Gingras, Anne‐Claude; Eling, Thomas E.; Sonenberg, Nahum

doi:10.1074/jbc.274.18.12925

Cited by 48 publications

(35 citation statements)

References 58 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The signaling pathways activated subsequent to increases in cellular ROS are unclear. Consistent with previous reports our data suggest that PGF 2α -induced VSMC hypertrophy is associated with the activation of ERK1/2-MAPK (15,16). In addition, we show that fluprostenol can activate Akt, GSK-3β, mTOR, p70 S6K , and PTEN in the A7r5 vascular smooth muscle cell line.…”

Section: Discussionsupporting

confidence: 93%

“…Recent studies using vascular smooth muscle cells have suggested that PGF 2α associated VSMC hypertrophy is mediated by NAD(P)H oxidase-derived reactive oxygen species (ROS) (14) while others have suggested that the extracellular regulated kinase 1/2 (ERK1/2) signaling pathway may be involved (15,16). However, the involvement of other upstream or parallel pathways has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

PGF2α-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN

Rice

Uddemarri

Desai

et al. 2008

Prostaglandins & Other Lipid Mediators

View full text Add to dashboard Cite

Prostaglandin F 2α (PGF2α) increases reactive oxygen species (ROS) and induces vascular smooth muscle cell (VSMC) hypertrophy by largely unknown mechanism(s). To investigate the signaling events governing PGF2α -induced VSMC hypertrophy we examined the ability of the PGF2α analog, fluprostenol to elicit phosphorylation of Akt, the mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70 S6k ), glycogen synthase kinase-3β (GSK-3β), phosphatase and tensin homolog (PTEN), extracellular signal-regulated kinase 1/2 (ERK1/2) and Jun N-terminal kinase (JNK) in growth arrested A7r5 VSMC. Fluprostenol-induced hypertrophy was associated with increased ROS, mTOR translocation from the nucleus to the cytoplasm, along with Akt, mTOR, GSK-3β, PTEN and ERK1/2 but not JNK phosphorylation. Whereas inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 blocked fluprostenol-induced changes in total protein content, pretreatment with rapamycin or with the ERK1/2-MAPK inhibitor UO126 did not. Taken together, these findings suggest that fluprostenol-induced changes in A7R5 hypertrophy involve mTOR translocation and occur through PI3K-dependent mechanisms.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

PGF2α-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN

Rice

Uddemarri

Desai

et al. 2008

Prostaglandins & Other Lipid Mediators

View full text Add to dashboard Cite

show abstract

“…PI3K Assay-PI3K activity was measured as described previously (34). Briefly, after appropriate treatments, cells were lysed in 1 ml of lysis buffer (20 mM HEPES, pH 7.4, 2 mM EGTA, 50 mM ␤-glycerophosphate, 1 mM dithiothreitol, 1 mM Na 3 VO 4 , 1% Triton X-100, 10% glycerol, 2 M leupeptin, 10 units/ml aprotinin, and 400 M PMSF) for 20 min on ice.…”

Section: Reagentsmentioning

confidence: 99%

“…Together, these findings demonstrate for the first time that PP2A mediates thiol-sensitive redox regulation of Akt and cell survival. Cell Culture-VSMC were isolated from the thoracic aortae of 200-to 300-g male Sprague-Dawley rats by enzymatic dissociation as described earlier (34). Cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% (v/v) heat-inactivated fetal bovine serum (FBS), 100 units/ml penicillin, and 100 g/ml streptomycin.…”

mentioning

confidence: 99%

N-Ethylmaleimide Inhibits Platelet-derived Growth Factor BB-stimulated Akt Phosphorylation via Activation of Protein Phosphatase 2A

Yellaturu¹,

Bhanoori²,

Neeli³

et al. 2002

Journal of Biological Chemistry

Self Cite

124

View full text Add to dashboard Cite

The redox state plays an important role in gene regulation. Thiols maintain the intracellular redox homeostasis. To understand the role of thiols in redox signaling, we have studied the effect of thiol alkylation on platelet-derived growth factor-BB (PDGF-BB)-induced cell survival events in vascular smooth muscle cells. PDGF-BB stimulated Akt phosphorylation predominantly at Ser-473. N-Ethylmaleimide (NEM), a thiol alkylating agent, blocked PDGF-BB-induced Akt phosphorylation without affecting its upstream phosphatidylinositol 3-kinase (PI3K). On the other hand, LY294002 and wortmannin, specific inhibitors of PI3K, prevented PDGF-BB-induced phosphorylation of Akt and its downstream effector molecules, p70S6K, ribosomal protein S6, 4E-BP1, and eIF4E. NEM also abrogated the phosphorylation of p70S6K, ribosomal protein S6, 4E-BP1, and eIF4E induced by PDGF-BB, suggesting that thiol alkylation interferes with the PI3K/Akt pathway at the level of Akt. In addition, NEM blocked PDGF-BBinduced phosphorylation of BAD and forkhead transcription factor FKHR-L1, and these events correlated with increased apoptosis. NEM alone and in concert with PDGF-BB increased reactive oxygen species (ROS) production and protein phosphatase 2A (PP2A) activity in VSMC. The inhibition of PDGF-BB-induced Akt phosphorylation by NEM was completely reversed by PP2A inhibitors fostriecin and okadaic acid, ceramide synthase inhibitor fumonisin B1, and ROS scavenger Nacetylcysteine (NAC). NAC also attenuated the apoptosis induced by NEM, alone or in combination with PDGF-BB. Together, these findings demonstrate for the first time that PP2A mediates thiol alkylation-dependent redox regulation of Akt and cell survival.The cellular redox state plays an important role in the regulation of gene expression in prokaryotes and eukaryotes (1-4). The following observations support this notion: 1) Oxidants regulate the activities of several transcription factors, including activator protein-1, nuclear factor kappa B, and p53 (5-7); 2) Oxidants are capable of activating several early response events, including stimulation of protein tyrosine phosphorylation, activation of mitogen-activated protein kinases and induction of expression of proto-oncogenes (8 -11); 3) Oxidants are produced acutely in response to various agents, including growth factors and cytokines in several cell types (12, 13), and a requirement for their production in the mitogenic effects of receptor tyrosine kinase and G protein-coupled receptor agonists has been demonstrated (14, 15); and 4) In addition to producing oxidants, cells also possess enzymatic and non-enzymatic mechanisms for their removal (16 -18), and this feature attests to the role of oxidants as second messenger molecules (19). Despite the growing body of information on the role of oxidants in the regulation of gene expression, the mechanisms by which these molecules transmit the extracellular signals from the plasma membrane to the nucleus are less clear. Thiols play a critical role in the reduction/oxidation reactions as w...

show abstract

“…The findings that eicosanoids, particularly the LOX products of arachidonic acid, mediate mitogen-induced signaling events via inhibition of GTPase activating proteins offer additional support for their role in cell growth (11,12,49). In addition to their role in the mitogenic signaling events cited above, some eicosanoids such as prostaglandin F 2␣ and 12(R)-hydroxy-5,8,14-eicosatrienoic acid induce the expression of angiogenic factors bFGF-2 and VEGF in rat aortic smooth muscle cells and rabbit limbal microvessel endothelial cells, respectively (50,51). In the present study we show for the first time that 5(S)-HETE induces the expression of bFGF-2 and, thereby, stimulates an autocrine growth in HMVEC, and this phenomenon is dependent on activation of Jak-2 and PI3-kinase.…”

Section: (S)-hete Stimulates Autocrine Growth In Hmvecmentioning

confidence: 99%

5(S)-Hydroxyeicosatetraenoic Acid Stimulates DNA Synthesis in Human Microvascular Endothelial Cells via Activation of Jak/STAT and Phosphatidylinositol 3-Kinase/Akt Signaling, Leading to Induction of Expression of Basic Fibroblast Growth Factor 2

Zeng¹,

Yellaturu²,

Neeli³

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

A Potential Role for Extracellular Signal-regulated Kinases in Prostaglandin F2α-induced Protein Synthesis in Smooth Muscle Cells

Cited by 48 publications

References 58 publications

PGF2α-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN

PGF2α-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN

N-Ethylmaleimide Inhibits Platelet-derived Growth Factor BB-stimulated Akt Phosphorylation via Activation of Protein Phosphatase 2A

5(S)-Hydroxyeicosatetraenoic Acid Stimulates DNA Synthesis in Human Microvascular Endothelial Cells via Activation of Jak/STAT and Phosphatidylinositol 3-Kinase/Akt Signaling, Leading to Induction of Expression of Basic Fibroblast Growth Factor 2

Contact Info

Product

Resources

About