Critical role for classical PKC in activating Akt by phospholipase A<sub>2</sub>-modified LDL in monocytic cells

Preiß, Stefan; Namgaladze, Dmitry; Brüne, Bernhard

doi:10.1016/j.cardiores.2006.12.019

Cited by 23 publications

(21 citation statements)

References 37 publications

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“…PKC␣ has been shown to directly phosphorylate Akt-1 at the Ser473 site in vitro (34). Another study shows that PKC␣ and PKC␤ are critical for PLA-LDL-induced Akt phosphorylation and survival in THP-1 monocytic cells (36). Enzastaurin (LY-317615), a PKC␤ inhibitor, inhibits the Akt pathway and induces apoptosis in multiple myeloma cell lines (37).…”

Section: Discussionmentioning

confidence: 98%

“…Also, various PKC isoenzymes have been shown to activate Akt (34). For example, PKC␣ and PKC␤ are critical for phospholipase-modified LDL (PLA-LDL)-induced Akt phosphorylation and survival in THP-1 monocytic cells (36). PKC␣ increases Akt-1 activity via Ser473 phosphorylation in response to insulin growth factor-1 (34) via a direct phosphorylation of Akt-1 (34).…”

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confidence: 99%

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Protein kinase Cδ regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation

Sud¹,

Wedgwood²,

Black³

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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In this study, we explore the roles of the delta isoform of PKC (PKCdelta) in the regulation of endothelial nitric oxide synthase (eNOS) activity in pulmonary arterial endothelial cells isolated from fetal lambs (FPAECs). Pharmacological inhibition of PKCdelta with either rottlerin or with the peptide, deltaV1-1, acutely attenuated NO production, and this was associated with a decrease in phosphorylation of eNOS at Ser1177 (S1177). The chronic effects of PKCdelta inhibition using either rottlerin or the overexpression of a dominant negative PKCdelta mutant included the downregulation of eNOS gene expression that was manifested by a decrease in both eNOS promoter activity and protein expression after 24 h of treatment. We also found that PKCdelta inhibition blunted Akt activation as observed by a reduction in phosphorylated Akt at position Ser473. Thus, we conclude that PKCdelta is actively involved in the activation of Akt. To determine the effect of Akt on eNOS signaling, we overexpressed a dominant negative mutant of Akt and determined its effect of NO generation, eNOS expression, and phosphorylation of eNOS at S1177. Our results demonstrated that Akt inhibition was associated with decreased NO production that correlated with reduced phosphorylation of eNOS at S1177, and decreased eNOS promoter activity. We next evaluated the effect of endogenously produced NO on eNOS expression by incubating FPAECs with the eNOS inhibitor 2-ethyl-2-thiopseudourea (ETU). ETU significantly inhibited NO production, eNOS promoter activity, and eNOS protein levels. Together, our data indicate involvement of PKCdelta-mediated Akt activation and NO generation in maintaining eNOS expression.

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Protein kinase Cδ regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation

Sud¹,

Wedgwood²,

Black³

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…For example, phospholipase activation within the low density lipoproteins (LDL) favors the formation of arterial plaques. Phospholipase can modify LDL and this confers a survival response towards oxidative stress which was found to be dependent upon the activation of several PKC isoforms [17]. There are other membrane lipids which interact with the C1 domain and activate either PKCγ or PKCε.…”

Section: Lipid Activation Signalsmentioning

confidence: 99%

Protein kinase C as a stress sensor

Barnett

Madgwick

Takemoto

2007

Cellular Signalling

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While there are many reviews which examine the group of proteins known as protein kinase C (PKC), the focus of this article is to examine the cellular roles of two PKCs that are important for stress responses in neurological tissues (PKCγ and ε) and in cardiac tissues (PKCε). These two kinases, in particular, seem to have overlapping functions and interact with an identical target, connexin 43 (Cx43), a gap junction protein which is central to proper control of signals in both tissues. While PKCγ and PKCε both help protect neural tissue from ischemia, PKCε is the primary PKC isoform responsible for responding to decreased oxygen, or ischemia, in the heart. Both do this through Cx43.It is clear that both PKCγ and PKCε are necessary for protection from ischemia. However, the importance of these kinases has been inferred from preconditioning experiments which demonstrate that brief periods of hypoxia protect neurological and cardiac tissues from future insults, and that this depends on the activation, translocation, or ability for PKCγ and/or PKCε to interact with distinct cellular targets, especially Cx43.This review summarizes the recent findings which define the roles of PKCγ and PKCε in cardiac and neurological functions and their relationships to ischemia/reperfusion injury. In addition, a biochemical comparison of PKC γ and PKC ε and a proposed argument for why both forms are present in neurological tissue while only PKC ε is present in heart, are discussed. Finally, the biochemistry of PKCs and future directions for the field are discussed, in light of this new information.

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“…It is known that cAMP has an inhibitory effect on the production of inflammatory mediators such as TNF-␣ (1) and reactive oxygen intermediate generation. Furthermore, Preiss et al (28) showed that PKC is critical for PLA-LDKinduced Akt/PKB phosphorylation and survival in thp-1 monocytic cells. The observation that prehypertensive and hypertensive SHR have renal inflammatory processes could be associated with the observation that these animals have higher PKC and lower PKA activities.…”

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confidence: 99%

Changes in angiotensin receptors expression play a pivotal role in the renal damage observed in spontaneously hypertensive rats

Landgraf

Wengert

Silva

et al. 2011

American Journal of Physiology-Renal Physiology

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The renal renin-angiotensin system plays a central role in the development of hypertension. The aim of this work was to verify the expression of angiotensin II receptors AT 1R and AT2R in the microsomal fraction of renal cortex and correlate this with the development of hypertension and renal damage in spontaneously hypertensive rats (SHR) using Wistar-Kyoto rats (WKY) as controls. AT 1R expression increased (126%) and AT 2R expression decreased (66%) in 4-wk-old SHR; AT2 expression decreased in 14-wk-old SHR (61%) compared with respective agematched WKY. These modifications were correlated to the increase in protein kinase C activity and decrease in protein kinase A activity. Four-week-old SHR showed large accumulations of macrophages in kidney glomerulus and the tubulointerstitial area, dense cortical collagen deposition, and arterial proliferative changes in the walls of arterioles and medium-sized vessels. Similar modifications were also observed in 14-wk-old SHR. Four-week-old SHR treated with losartan (30 mg·kg Ϫ1 ·day Ϫ1 ) or hydralazine (15 and 30 mg·kg Ϫ1 ·day Ϫ1 ) by gavage for 10 wk did not develop hypertension. The decrease in AT 2R expression and renal damage observed in SHR remained even after treatment with hydralazine. On the other hand, losartan treatment prevented the modifications observed in 14-wk-old SHR, indicating that renal injuries are caused specifically by AT1 rather than an increase in blood pressure. Our results indicate that the imbalance in AT1R and AT2R expression is associated with an inflammatory process that contributes to renal injury in adult SHR and to the development of hypertension.renin-angiotensin system; kidney; angiotensin II receptors; inflammation THE KEY ROLE OF THE KIDNEY in primary hypertension pathogenesis has been proposed based on measurements of renal function and renal transplantation studies in spontaneously hypertensive rats (SHR) and human patients (10,14). Renal damage is commonly caused by hypertension, which is a key to morbidity and mortality (23). On the other hand, renal damage could be involved in the genesis of hypertension, showing the dangerous loop in this correlation.Some studies showed functional alterations in tissues that precede the development of hypertension (17,27,32). Based on these observations, one attractive hypothesis is that asymptomatic alterations in renal function at an early stage could be contributed to development of the primary hypertension. Identification of the mechanisms responsible for these events becomes very attractive as an early marker of primary hypertension development and in prevention of hypertension. One candidate could be the renin-angiotensin system (RAS), which plays an important role in renal function and regulation of blood pressure.The effects of angiotensin II (ANG II) are mediated mainly by two receptors: angiotensin type 1 receptor (AT 1 R) or angiotensin type 2 receptor (AT 2 R) (11). AT 1 R activation is involved in vasoconstriction and proinflammatory action; AT 2 R counteracts the effects triggered...

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Critical role for classical PKC in activating Akt by phospholipase A₂-modified LDL in monocytic cells

Abstract: We show that PKCalpha and PKCbeta are critical for PLA-LDL-induced Akt phosphorylation and survival in THP-1 monocytic cells.

Cited by 23 publications

References 37 publications

Protein kinase Cδ regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation

Protein kinase Cδ regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation

Protein kinase C as a stress sensor

Changes in angiotensin receptors expression play a pivotal role in the renal damage observed in spontaneously hypertensive rats

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Critical role for classical PKC in activating Akt by phospholipase A2-modified LDL in monocytic cells

Abstract: We show that PKCalpha and PKCbeta are critical for PLA-LDL-induced Akt phosphorylation and survival in THP-1 monocytic cells.

Cited by 23 publications

References 37 publications

Protein kinase Cδ regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation

Protein kinase Cδ regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation

Protein kinase C as a stress sensor

Changes in angiotensin receptors expression play a pivotal role in the renal damage observed in spontaneously hypertensive rats

Contact Info

Product

Resources

About

Critical role for classical PKC in activating Akt by phospholipase A₂-modified LDL in monocytic cells