Angiotensin II and Cell Cycle Regulation

Wolf, Günter; Wenzel, Ulrich

doi:10.1161/01.hyp.0000120963.09029.ca

Cited by 67 publications

(46 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In tubular cells Ang II leads to phosphorylation of the mitogen-activated protein kinases ERK1/2 that phosphorylate p27 kip at serine residues. The p27 kip phosphorylation at serine/theonine residues leads, in contrast to tyrosine phosphorylation, to an increased stability and less degradation through the ubiquitin pathway (Wolf & Wenzel 2003). Therefore, it is possible that Ang IIstimulated PKC-z activation has a similar role in the processes that regulate p27 kip stability, although we can only speculate at this point.…”

Section: Discussionmentioning

confidence: 89%

See 1 more Smart Citation

Angiotensin II does not stimulate proliferation of rat thyroid PC Cl3 cell line

Romano¹,

Muscella²,

Storelli³

et al. 2006

Journal of Endocrinology

View full text Add to dashboard Cite

In PC Cl3 cells, a rat thyroid cell line, angiotensin (Ang II) activates the atypical protein kinase C-z (PKC-z) and the extracellular signal-regulated kinase (ERK) pathways. We here studied the Ang II effects on PC Cl3 cell proliferation. It was found that Ang II: (1) induced the phosphorylation of protein kinase B (PKB), (2) induced the growth-related early gene c-fos expression, (3) enhanced the cyclin E and p27 kip expression, (4) had no effects on Cdk2, and (5) did not affect the transition from G0/G1 to S phase. Inhibition of phosphoinositide-3kinase by LY294002 further increased the effect of Ang II on p27 kip induction, whilst PKCs inhibition by GF109203X decreased such effect. The role of PKC-z was recognized by the use of a synthetic myristoylated peptide with sequences based on the endogenous PKC-z pseudosubstrate and by PKC-z downregulation using the small interfering RNA (siRNA). Insulin had a replicating effect on PC Cl3 cells, induced the phosphorylation of PKB, decreased p27 kip expression and had no effect on the PKC-z cytosol-to-membrane translocation. PC Cl3 cell proliferation was induced more potently by simultaneous stimulation with insulin and Ang II than by stimulation with insulin alone, and the effect on p27 kip expression was similar to that obtained with insulin only. These observations demonstrate that in PC Cl3 cells Ang II causes a block in G1 phase, although both ERK and PKB pathways are activated, and this effect may be due to the upregulation of p27 kip and PKC-z operativity.

show abstract

Section: Discussionmentioning

confidence: 89%

“…In contrast, cells undergoing Ang II-mediated hypertrophy, apoptosis, and differentiation are arrested in the G1 phase (Wolf & Wenzel 2003).…”

Section: Introductionmentioning

confidence: 96%

Angiotensin II does not stimulate proliferation of rat thyroid PC Cl3 cell line

Romano¹,

Muscella²,

Storelli³

et al. 2006

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…AngII-induced tubular hypertrophy, although initially an adaptive response to loss of functional nephrons, is over the long term maladaptive and likely fosters development of tubular atrophy and interstitial fibrosis. Moreover, AngII induces apoptosis under certain conditions in vivo and in vitro (39). Experimental evidence suggests that AT 1 and AT 2 receptors are involved in this effect.…”

Section: Growth Effects and Apoptosismentioning

confidence: 99%

“…In contrast, the peptide induces hypertrophy of proximal tubular cells by a p27 Kip1 -mediated cell-cycle arrest (38,39). Proliferation of glomerular cells and fibroblasts could enhance structural renal damage and fibrosis.…”

Section: Growth Effects and Apoptosismentioning

confidence: 99%

Renin-Angiotensin-Aldosterone System and Progression of Renal Disease

Rüster

Wolf

2006

Journal of the American Society of Nephrology

Self Cite

403

320

View full text Add to dashboard Cite

Inhibition of the renin-angiotensin-aldosterone system (RAAS) is one of the most powerful maneuvers to slow progression of renal disease. Angiotensin II (AngII) has emerged in the past decade as a multifunctional cytokine that exhibits many nonhemodynamic properties, such as acting as a growth factor and profibrogenic cytokine, and even having proinflammatory properties. Many of these deleterious functions are mediated by other factors, such as TGF-␤ and chemoattractants that are induced in the kidney by AngII. Moreover, understanding of the RAAS has become much more complex in recent years with the identification of novel peptides (e.g., AngIV) that could bind to specific receptors, elucidating deleterious effects, and non-angiotensin-converting enzyme (ACE)-mediated generation of AngII. The ability of renal cells to produce AngII in a concentration that is much higher than what is found in the systemic circulation and the observation that aldosterone may be engaged directly in profibrogenic processes independent of hypertension have added to the complexity of the RAAS. Even renin has now been identified to have a "life on its own" and mediates profibrotic effects via binding to specific receptors. Finally, drugs that are used to block the RAAS, such as ACE inhibitors or certain AngII type 1 receptor antagonists, may have properties on cells independent of AngII (ACE inhibitor-mediated outside-inside signaling and peroxisome proliferatoractivated receptor-␥ stimulatory effects of certain sartanes). Although blockade of the RAAS with ACE inhibitors, AngII type 1 receptor antagonists, or the combination of both should be part of every strategy to slow progression of renal disease, a better understanding of the novel aspects of the RAAS should contribute to the development of innovative strategies not only to completely halt progression but also to induce regression of human renal disease.

show abstract

“…As a corollary, consumption of ACE inhibitors during pregnancy has been shown to result in kidney malformation, mainly through defective angiogenesis/tubulogenesis. Thus, Ang II and the RAAS contribute to normal growth and development of the nephron through an interplay of AT 1 R-and AT 2 R-mediated effects and has additional roles in cell-cycle progression (369).…”

Section: Raas Expression In Developing and Adult Kidneysmentioning

confidence: 99%