Intracellular free Ca2+ in the cell cycle in human fibroblasts: transitions between G1 and G0 and progression into S phase.

Wahl, Michael J.; Gruenstein, Eric

doi:10.1091/mbc.4.3.293

Cited by 38 publications

(26 citation statements)

References 28 publications

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“…Chelating external Ca 2ϩ by EGTA prevents substance P-induced proliferation of cultured rat cardiac fibroblasts (43). In human fibroblasts, it has been reported that Ca 2ϩ influx is essential for the proliferation, and intracellular Ca 2ϩ is required for cell cycle progression from G1/G0 to S phase (64). We have recently shown that human cardiac fibroblasts contain several TRPC-mediated Ca 2ϩ influx pathways, and TGF-␤ 1 enhances the Ca 2ϩ influx pathways requiring Ca 2ϩ signals for its effect on fibroblast proliferation (35).…”

Section: Discussionmentioning

confidence: 99%

Effects of methylglyoxal on human cardiac fibroblast: roles of transient receptor potential ankyrin 1 (TRPA1) channels

Oguri

Nakajima

Yamamoto

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Effects of methylglyoxal on human cardiac fibroblast: roles of transient receptor potential ankyrin 1 (TRPA1) channels. Am J Physiol Heart Circ Physiol 307: H1339 -H1352, 2014. First published August 29, 2014; doi:10.1152/ajpheart.01021.2013.-Cardiac fibroblasts contribute to the pathogenesis of cardiac remodeling. Methylglyoxal (MG) is an endogenous carbonyl compound produced under hyperglycemic conditions, which may play a role in the development of pathophysiological conditions including diabetic cardiomyopathy. However, the mechanism by which this occurs and the molecular targets of MG are unclear. We investigated the effects of MG on Ca 2ϩ signals, its underlying mechanism, and cell cycle progression/cell differentiation in human cardiac fibroblasts. The conventional and quantitative real-time RT-PCR, Western blot, immunocytochemical analysis, and intracellular Ca 2ϩ concentration [Ca 2ϩ ]i measurement were applied. Cell cycle progression was assessed using the fluorescence activated cell sorting. MG induced Ca 2ϩ entry concentration dependently. Ruthenium red (RR), a general cation channel blocker, and HC030031, a selective transient receptor potential ankyrin 1 (TRPA1) antagonist, inhibited MG-induced Ca 2ϩ entry. Treatment with aminoguanidine, a MG scavenger, also inhibited it. Allyl isothiocyanate, a selective TRPA1 agonist, increased Ca 2ϩ entry. The use of small interfering RNA to knock down TRPA1 reduced the MGinduced Ca 2ϩ entry as well as TRPA1 mRNA expression. The quantitative real-time RT-PCR analysis showed the prominent existence of TRPA1 mRNA. Expression of TRPA1 protein was confirmed by Western blotting and immunocytochemical analyses. MG promoted cell cycle progression from G0/G1 to S/G2/M, which was suppressed by HC030031 or RR. MG also enhanced ␣-smooth muscle actin expression. The present results suggest that methylglyoxal activates TRPA1 and promotes cell cycle progression and differentiation in human cardiac fibroblasts. MG might participate the development of pathophysiological conditions including diabetic cardiomyopathy via activation of TRPA1.human cardiac fibroblast; transient receptor potential ankyrin 1 channels; methylglyoxal CARDIAC FIBROBLASTS ARE THE predominant secretary cell types located within the extracellular matrix (ECM) (18), which account for 60ϳ70% of the cells in human hearts and play a key role in regulating normal myocardial function and in the adverse myocardial remodeling that occurs with hypertension, heart failure, and myocardial infarction (12, 71). Many of the functional effects of cardiac fibroblasts are mediated through differentiation of cardiac fibroblasts to myofibroblasts phenotype that expresses contractile proteins such as ␣-smooth muscle actin (␣-SMA), and they consequently exhibit increased migratory and proliferative properties. Cardiac fibroblasts also take a part in the maintenance of myocardial function by producing the type I and type III collagens and by secreting growth factors (48), and a key source of components of the ECM that regulat...

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Section: Discussionmentioning

confidence: 99%

Effects of methylglyoxal on human cardiac fibroblast: roles of transient receptor potential ankyrin 1 (TRPA1) channels

Oguri

Nakajima

Yamamoto

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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“…This incomplete inhibition of fibroblast proliferation suggest that calcyclin plays a role in modulating the intracellular signaling events necessary for cells to divide. Thus, calcyclin could potentially play a role in calcium homeostasis and signaling of intracellular calcium transients required at various control points of the cell cycle in mitogen stimulated cells [Wahl and Gruenstein, 1993]. Likewise, pulmonary fibroblasts respond to strain with an increase in intracellular calcium levels via gadolinium sensitive calcium channels and release of the mitogen, PDGF.…”

Section: Calcyclin Attenuates Pulmonary Fibroblast Proliferationmentioning

confidence: 99%

Calcyclin (S100A6) regulates pulmonary fibroblast proliferation, morphology, and cytoskeletal organization in vitro

Breen

Tang

2003

J of Cellular Biochemistry

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Calcyclin (S100A6) is a member of the S100A family of calcium binding proteins. While the precise function of calcyclin is unknown, calcyclin expression is associated with cell proliferation and calcyclin is expressed in several types of cancer phenotypes. In the present study, the functional role of calcyclin was further elucidated in pulmonary fibroblasts. Antisense S100A6 RNA expression inhibited serum and mechanical strain-induced fibroblast proliferation. This attenuated proliferative response was accompanied by a flattened, spread cell morphology, and disruption of tropomyosin labeled microfilaments. Changes in cytoskeletal organization did not correspond with a decrease in tropomyosin levels. These observations suggest a role for calcyclin in modulating calcium dependent signaling events that regulate progression through the cell cycle. J. Cell. Biochem. 88: 848-854, 2003.

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“…Mitogenic stimulation of PLC␥ leads to a rapid and transient increase of intracellular calcium through the second messenger inositol triphosphate (31), as well as the generation of diacyl glycerol (DAG) with subsequent activation of PKC (32). Although the role of this calcium "spike" in mitogenesis is poorly character-ized (31,33,34), increases in calcium and DAG result in activation of both the conventional and novel PKCs. Although simultaneous activation of PI3K I A and increase of intracellular calcium, via the PLC␥/DAG/1,4,5-inositol triphosphate pathway, is observed in many cell types, little attention has been given to the interactions between both systems.…”

Section: Phosphatidylinositol 3-kinase I a (Pi3kmentioning

confidence: 99%

Differential Regulation by Calcium Reveals Distinct Signaling Requirements for the Activation of Akt and p70S6k

Conus¹,

Hemmings²,

Pearson³

1998

Journal of Biological Chemistry

112

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Activation of the phosphatidylinositol 3-kinase (PI3K) plays an important role in the mitogenic response of many cell types. Recently, two serine/threonine kinases Akt and p70S6k have been identified as physiological targets of PI3K. Observations that expression of activated forms of Akt led to the activation of p70 S6k implied Akt might mediate mitogenic signaling through activation of p70S6k . To clarify the relationship between signaling through these two kinases, we have examined their regulation by various mitogenic stimuli. In this study we have focused on the role of calcium in the regulation of each kinase in Balb/c-3T3 fibroblasts. Depletion of intracellular calcium stores by EGTA pretreatment has no effect on growth factor-induced Akt activation but completely abolishes p70S6k stimulation. Increase of intracellular calcium induced by ionomycin or thapsigargin results in a full activation of p70S6k , whereas little or no activation of Akt is observed. Furthermore, although PI3K in anti-phosphotyrosine immunoprecipitates is only very weakly activated by ionomycin, the calcium-induced stimulation of p70 S6k is completely inhibited by the specific PI3K inhibitor wortmannin. We conclude Akt and p70S6k lie on separate signaling pathways. Activation of signaling to Akt is insufficient for the activation of p70 S6k , which can be achieved independently of Akt. p70S6k requires a separate calcium-dependent and wortmannin-sensitive process that is likely to be independent of type I A PI3K family members.

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Intracellular free Ca2+ in the cell cycle in human fibroblasts: transitions between G1 and G0 and progression into S phase.

Cited by 38 publications

References 28 publications

Effects of methylglyoxal on human cardiac fibroblast: roles of transient receptor potential ankyrin 1 (TRPA1) channels

Effects of methylglyoxal on human cardiac fibroblast: roles of transient receptor potential ankyrin 1 (TRPA1) channels

Calcyclin (S100A6) regulates pulmonary fibroblast proliferation, morphology, and cytoskeletal organization in vitro

Differential Regulation by Calcium Reveals Distinct Signaling Requirements for the Activation of Akt and p70S6k

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