Regulation of Mitogen-activated Protein Kinase Phosphatase-1 Induction by Insulin in Vascular Smooth Muscle Cells

Begum, Najma; Ragolia, Louis; Rienzie, Jennifer; McCarthy, Marguerite; Duddy, Noreen

doi:10.1074/jbc.273.39.25164

Cited by 88 publications

(29 citation statements)

References 39 publications

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“…In addition, protein kinase C and p38 MAPK activation have been reported to cause an increase in PG formation (45), and elevated protein kinase C levels have also been reported in VSMCs of diabetic rats (46). Similarly, we have observed the decreased activation of PI3K (3) and increased p38 MAPK activation and phosphorylation in VSMCs isolated from SHR rats (47). Our present results suggest that when VSMCs are in a hyperproliferative state, such as in serum-induced SHR or upon differentiation, L-PGDS expression is elevated to inhibit cell proliferation and stimulate cellular apoptosis.…”

Section: Figsupporting

confidence: 60%

Prostaglandin D2 Synthase Inhibits the Exaggerated Growth Phenotype of Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells

Ragolia

Palaia

Paric

et al. 2003

Journal of Biological Chemistry

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Lipocalin-type prostaglandin D 2 synthase (L-PGDS)has recently been linked to a variety of pathophysiological cardiovascular conditions including hypertension and diabetes. In this study, we report on the 50% increase in L-PGDS protein expression observed in vascular smooth muscle cells (VSMC) isolated from spontaneously hypertensive rats (SHR). L-PGDS expression also increased 50% upon the differentiation of normotensive control cells (WKY, from Wistar-Kyoto rats). In addition, we demonstrate differential effects of L-PGDS treatment on cell proliferation and apoptosis in VSMCs isolated from SHR versus WKY controls. L-PGDS (50 g/ml) was able to significantly inhibit VSMC proliferation and DNA synthesis and induce the apoptotic genes bax, bcl-x, and ei24 in SHR but had no effect on WKY cells. Hyperglycemic conditions also had opposite effects, in which increased glucose concentrations (20 mM) resulted in decreased L-PGDS expression in control cells but actually stimulated L-PGDS expression in SHR. Furthermore, we examined the effect of L-PGDS incubation on insulin-stimulated Akt, glycogen synthase kinase-3␤ (GSK-3␤), and ERK phosphorylation. Unexpectedly, we found that when WKY cells were pretreated with L-PGDS, insulin could actually induce apoptosis and failed to stimulate Akt/GSK-3␤ phosphorylation. Insulin-stimulated ERK phosphorylation was unaffected by L-PGDS pretreatment in both cell lines. We propose that L-PGDS is involved in the balance of VSMC proliferation and apoptosis and in the increased expression observed in the hypertensive state is an attempt to maintain a proper equilibrium between the two processes via the induction of apoptosis and inhibition of cell proliferation.

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Section: Figsupporting

confidence: 60%

Prostaglandin D2 Synthase Inhibits the Exaggerated Growth Phenotype of Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells

Ragolia

Palaia

Paric

et al. 2003

Journal of Biological Chemistry

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“…Hypertension Is Accompanied by Increased ROK-␣/IRS-1 Association and Inhibition of Insulin Signaling-Our earlier studies have shown that VSMCs isolated from SHR exhibit insulin resistance in terms of PI3-kinase activation, iNOS induction, as well as MBP activation when compared with Wistar Kyoto (WKY) (29). In contrast, the growth-mediating effects of insulin were enhanced in these cells due to sustained MAPK activation (30).…”

Section: Insulin and Dominantmentioning

confidence: 98%

“…Insulin treatment resulted in a 2-fold increase in cGMP-independent cGK I activity over basal (Fig. 6B), presumably due to endogenous production of cGMP by insulin (29,30). Thrombin treatment did not alter cGK I activity when present alone nor did it interfere with the effect of insulin when added after insulin treatment.…”

Section: Expression Of Cgk I␣ Inactivates Rho Kinase Abolishes Thrommentioning

confidence: 98%

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Active Rho Kinase (ROK-α) Associates with Insulin Receptor Substrate-1 and Inhibits Insulin Signaling in Vascular Smooth Muscle Cells

Begum

Sandu

et al. 2002

Journal of Biological Chemistry

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Small GTPases of the Rho family are well known intracellular signaling proteins that act as molecular switches to control actin cytoskeleton organization in many cell types including smooth muscle (1-4). Recent studies indicate that RhoA-dependent signaling pathway controls vascular smooth muscle cell functions such as contraction, migration, and proliferation (5-6). In VSMCs, 1 the contractile effect of RhoA results from the activation of Rho-dependent kinase (ROK-␣), which phosphorylates the regulatory subunit of myosin light chain phosphatase (MBS) and thereby inhibits the phosphatase activity (7-8), thus allowing an increase in the level of phosphorylated myosin light chain and contraction at a constant intracellular calcium level [Ca 2ϩ ] i (9). This phenomenon is defined as Ca 2ϩ sensitization (10). ROK-␣ and another isoform Rho kinase, ROCK1, are serine/ threonine protein kinases that contain an amino-terminal catalytic kinase domain, a central coiled-coil domain in which Rho/GTP binds, and a carboxyl-terminal pleckstrin homology (PH) domain that is split by a cysteine-rich region (11-12). Insulin receptor substrate proteins (IRS) also contain an amino-terminal PH domain and phosphotyrosine binding domain domain. The PH domain is required for efficient phosphorylation of IRS-1 by the insulin receptor (13-15). In addition, IRS-1 also interacts with 14-3-3 proteins, a process apparently dependent on serine phosphorylation of IRS-1 (16).Recent studies from our laboratory (17) have shown that insulin rapidly stimulates myosin-associated phosphatase (MBP) activity by causing a site-specific decrease in MBS T695 phosphorylation by inactivating thrombin-stimulated Rho and one of its downstream effectors, Rho kinase. Furthermore, inhibition of PI3-kinase, nitric-oxide synthase (NOS), and cGMP signaling pathways abolished insulin-stimulated MBP activation suggesting the involvement of these signaling pathways in MBP activation (18). Thus, insulin stimulates MBP in VSMCs by activating the NO/cGMP signaling pathway that also inactivates Rho/Rho kinase (17). The effects of insulin on MBP activation and vasorelaxation were severely impaired in VSMCs isolated from diabetic Goto-Kakizaki rats and spontaneous hypertensive rats (SHR) due to defective IRS-1/PI3-kinase signaling as well as up-regulation of Rho kinase activity (18,19). These observations prompted us to explore in detail potential interactions between Rho signaling and insulin signaling pathways.In the present study, VSMCs were infected with an activated RhoA V14 , dominant negative RhoA N19 , and cGK I␣. We examined the effects of insulin and thrombin on ROK-␣/IRS-1 association, IRS-1 tyrosine phosphorylation, IRS-1/p85 PI3-kinase association, and PI3-kinase activation and its impact on MBS T695 site-specific phosphorylation and MBP activation. * This work was supported by a American Heart Association Established Investigator grant, medical education funds from Winthrop University Hospital, and by Deutsche Forschungsgemeinschaft Grant SFB355. The costs of ...

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“…Gu et al, 2000). PKG has also been shown to modulate the activity of radio-responsive transcription factors (AP-1, CREB, TP53) and the expression of several genes whose expression is also stimulated by radiation, including JUN-B, c-FOS, MKP-1, cyclooxygenase-2, tumor necrosis factor-alpha and P21 Waf1/Cip1 (Haby et al, 1994;Gudi et al, 1996;Sciorati et al, 1997;Begum et al, 1998;Collins and Uhler, 1999;Gertzberg et al, 2000;Gu et al, 2000;Brune et al, 2001;Pfeilschifter et al, 2001). …”

Section: S-glutathiolation Modulation Of Protein Functionmentioning

confidence: 99%

Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms

2003

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In the past few years, nuclear DNA damage-sensing mechanisms activated by ionizing radiation have been identified, including ATM/ATR and the DNA-dependent protein kinase. Less is known about sensing mechanisms for cytoplasmic ionization events and how these events influence nuclear processes. Several studies have demonstrated the importance of cytoplasmic signaling pathways in cytoprotection and mutagenesis. For cytoplasmic signaling, radiation-stimulated reactive oxygen species (ROS) and reactive nitrogen species (RNS) are essential activators of these pathways. This review summarizes recent studies on the chemistry of radiation-induced ROS/ RNS generation and emphasizes interactions between ROS and RNS and the relative roles of cellular ROS/ RNS generators as amplifiers of the initial ionization events. Cellular mechanisms for regulating ROS/RNS levels are discussed. The mechanisms by which cells sense ROS/RNS are examined in terms of how ROS/RNS modify protein structure and function, for example, interactions with metal-thiol clusters, protein tyrosine nitration, protein cysteine oxidation, S-thiolation and Snitrosylation. We propose that radiation-induced ROS are the initiators and that nitric oxide (NO ) or derivatives are the effectors activating these signal transduction pathways. In responding to cellular ionization events, the cell converts an oxidative signal to a nitrosative one because ROS are too reactive and unspecific in their reactions for regulatory purposes and the cell is equipped to precisely modulate NO levels.

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Regulation of Mitogen-activated Protein Kinase Phosphatase-1 Induction by Insulin in Vascular Smooth Muscle Cells

Cited by 88 publications

References 39 publications

Prostaglandin D2 Synthase Inhibits the Exaggerated Growth Phenotype of Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells

Prostaglandin D2 Synthase Inhibits the Exaggerated Growth Phenotype of Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells

Active Rho Kinase (ROK-α) Associates with Insulin Receptor Substrate-1 and Inhibits Insulin Signaling in Vascular Smooth Muscle Cells

Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms

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