Ca2+/Calmodulin-Dependent Protein Kinase II Mediates Platelet-Derived Growth Factor-Induced Human Hepatic Stellate Cell Proliferation

An, Ping; Tian, Ye; Dai, Jingxing; Minkai, Chen; Luo, Haitao

doi:10.1007/s10620-011-2014-2

Cited by 10 publications

(4 citation statements)

References 37 publications

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“…There are several reports that Ca 2+ influences proliferation and apoptosis in activated HSCs. 22,23) , did not affect the suppressive effect of 3 mM caffeine on HSC activation. It is plausible that Ca 2+ is not involved in the effect of caffeine, at least at the 3 mM level, on HSC activation.…”

Section: Discussionmentioning

confidence: 73%

Caffeine Suppresses the Activation of Hepatic Stellate Cells cAMP-Independently by Antagonizing Adenosine Receptors

Yamaguchi

Nishiyama

Nakamura

et al. 2017

Biological & Pharmaceutical Bulletin

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During liver injury, hepatic stellate cells (HSCs) are activated by various cytokines and transdifferentiated into myofibroblast-like activated HSCs, which produce collagen, a major source of liver fibrosis. Therefore, the suppression of HSC activation is regarded as a therapeutic target for liver fibrosis. Several epidemiological reports have revealed that caffeine intake decreases the risk of liver disease. In this study, therefore, we investigated the effect of caffeine on the activation of primary HSCs isolated from mice. Caffeine suppressed the activation of HSC in a concentration-dependent manner. BAPTA-AM, an intracellular Ca 2 chelator, had no effect on the caffeine-induced suppression of HSC activation. None of the isoformselective inhibitors of phosphodiesterase1 to 5 affected changes in the morphology of HSC during activation, whereas CGS-15943, an adenosine receptor antagonist, inhibited them. Caffeine had no effect on intracellular cAMP level or on the phosphorylation of extracellular signal-regulated kinase (ERK)1/2. In contrast, caffeine significantly decreased the phosphorylation of Akt1. These results suggest that caffeine inhibits HSC activation by antagonizing adenosine receptors, leading to Akt1 signaling activation.

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Section: Discussionmentioning

confidence: 73%

Caffeine Suppresses the Activation of Hepatic Stellate Cells cAMP-Independently by Antagonizing Adenosine Receptors

Yamaguchi

Nishiyama

Nakamura

et al. 2017

Biological & Pharmaceutical Bulletin

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“…The CaMKII-specific inhibitor KN-93 has been found to significantly increase p 53 expression to regulate the cell cycle in myofibroblastic hepatic stellate cells (HSCs). 25) One of the key contributions of p53 to apoptosis is the upregulation of proapoptotic Bax gene expression and the downregulation of anti-apoptotic Bcl-2 gene expression. 26) Bax and p53 directly initiate the translocalization of pro-apoptotic members to mitochondria and activate them to trigger mitochondrial leakage.…”

Section: Discussionmentioning

confidence: 99%

Taurine Protects Primary Neonatal Cardiomyocytes Against Apoptosis Induced by Hydrogen Peroxide

Wang

Liu

et al. 2018

Int. Heart J.

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SummaryThe aim of this study was to investigate the effects of taurine (Tau) on primary cultured neonatal myocardial cells treated with hydrogen peroxide (H2O2) and the underlying mechanism. Primary cardiac myocytes from neonatal Wistar rats were pre-incubated with Tau, and its effects on cell viability and expression of CaM, CaM-KII, p53, Bcl-2, and Bax were examined. Tau enhanced the viability of myocardial cells, decreased apoptosis, and alleviated the intracellular calcium overload, especially at dosages of 40 or 80 mM (P < 0.01 or P < 0.001, respectively). Moreover, Tau could inhibit the H2O2-induced decrease in CamKII and CaM expression at both the mRNA and protein levels. The pattern of CaMKII expression was consistent with that of the anti-apoptotic protein Bcl-2, but contrasted the pattern of the pro-apoptotic proteins p53 and Bax. Thus, our results show that Tau protects myocardial cells against damage caused by H2O2 exposure, suggesting that it might play a role in the mitochondrial apoptotic pathway by upregulating the expression of CaMKII to rescue myocardial cells. However, the underlying mechanism still needs to be investigated. In addition, we tested the protective effect of taurine on cardiac myocytes, and the effect of taurine on another model, specifically an animal model. (Int Heart J 2018; 59: 190-196)

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“…Homomeric ASIC1a has also been reported to conduct Ca 2+ ions. [Ca 2+ ]i is important in mediating HSCs activation and stimulating contractility of HSCs (Ping et al, ). Our studies show that when ASICs were blocked, α‐SMA, a marker of transdifferentiation, was significantly reduced in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of ASICs reduces rat hepatic stellate cells activity and liver fibrosis: An in vitro and in vivo study

Pan

Wu²,

Wang³

et al. 2014

Cell Biology International

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Hepatic fibrosis is a chronic inflammation-associated disease, which is involved in the infiltration of inflammatory cells and releasing of proinflammatory cytokines. In the pathological process, protons are released by damaged cells and acidosis is considered to play a critical role in cell injury. Although the underlying mechanism (s) remain ill-defined, ASICs (acid-sensing ion channels) are assumed to be involved in this process. The diuretic, amiloride, is neuroprotective in models of cerebral ischemia, a property attributable to the inhibition of central ASICs by the drug. However, the effect of inhibition of ASICs by amiloride in the liver fibrotic process remains unclear. We found that amiloride (25, 50, or 100 μM) could restrain acid-induced HSCs at pH6 in vitro. In vivo experiments showed that amiloride could significantly alleviate liver injury, decreasing levels of profibrogenic cytokines, collagen deposition, and reducing pathological tissue damage. In summary, amiloride inhibits hepatic fibrosis in vivo and in vitro, which is probably associated with the downregulation of ASICs.

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Ca2+/Calmodulin-Dependent Protein Kinase II Mediates Platelet-Derived Growth Factor-Induced Human Hepatic Stellate Cell Proliferation

Abstract: We confirmed that CaMKII mediated PDGF-induced human HSC proliferation through ERK1/2 but not the JNK mechanism. Our study shed light on CaMKII as a crucial signal in PDGF-activated HSCs and a potential therapeutic point in hepatic fibrosis.

Cited by 10 publications

References 37 publications

Caffeine Suppresses the Activation of Hepatic Stellate Cells cAMP-Independently by Antagonizing Adenosine Receptors

Caffeine Suppresses the Activation of Hepatic Stellate Cells cAMP-Independently by Antagonizing Adenosine Receptors

Taurine Protects Primary Neonatal Cardiomyocytes Against Apoptosis Induced by Hydrogen Peroxide

Inhibition of ASICs reduces rat hepatic stellate cells activity and liver fibrosis: An in vitro and in vivo study

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