Lysophosphatidic acid induces reactive oxygen species generation by activating protein kinase C in PC-3 human prostate cancer cells

Lin, Cheng-Tao; Lin, Chuan-En; Lin, Yueh‐Chien; Ju, Tsai-Kai; Huang, Yuan‐Li; Lee, Ming-Shyue; Chen, Jiun‐Hong; Lee, Hsinyu

doi:10.1016/j.bbrc.2013.09.104

Cited by 28 publications

(30 citation statements)

References 31 publications

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“…It has been well characterized that LPA induces ROS via the phospholipase C/PKC/NOX pathway (19,20). Hence, we hypothesized that ROS could specifically augment total TAZ levels.…”

Section: H 2 O 2 Elevates Total Protein Levels Of Taz and Increasesmentioning

confidence: 96%

“…LPA has been demonstrated previously to induce elevation of superoxide (O 2 . ) via the phospholipase C/PKC/NOX pathway in cancer cell lines (19,20). To corroborate LPA-induced ROS elevation, we treated HEK 293T cells with increasing concentrations of LPA for 1 h and quantified superoxide generation using DHE.…”

Section: H 2 O 2 -Mediated Activation Of Taz Depends On S-glutathionymentioning

confidence: 99%

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Cysteine S-Glutathionylation Promotes Stability and Activation of the Hippo Downstream Effector Transcriptional Co-activator with PDZ-binding Motif (TAZ)

Gandhirajan

Jain

Walla

et al. 2016

Journal of Biological Chemistry

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Transcriptional co-activator with PDZ-binding motif (TAZ) and Yes-associated protein (YAP) are critical transcriptional coactivators downstream of the Hippo pathway involved in the regulation of organ size, tissue regeneration, proliferation, and apoptosis. Recent studies suggested common and distinct functions of TAZ and YAP and their diverse impact under several pathological conditions. Here we report differential regulation of TAZ and YAP in response to oxidative stress. H 2 O 2 exposure leads to increased stability and activation of TAZ but not of YAP. H 2 O 2 induces reversible S-glutathionylation at conserved cysteine residues within TAZ. We further demonstrate that TAZ S-glutathionylation is critical for reactive oxygen species (ROS)-mediated, TAZ-dependent TEA domain transcription factor (TEAD) trans-activation. Lysophosphatidic acid, a physiological activator of YAP and TAZ, induces ROS elevation and, subsequently, TAZ S-glutathionylation, which promotes TAZmediated target gene expression. TAZ expression is essential for renal homeostasis in mice, and we identify basal TAZ S-glutathionylation in murine kidney lysates, which is elevated during ischemia/reperfusion injury in vivo. This induced nuclear localization of TAZ and increased expression of connective tissue growth factor. These results describe a novel mechanism by which ROS sustains total cellular levels of TAZ. This preferential regulation suggests TAZ to be a redox sensor of the Hippo pathway.

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“…It has been well characterized that LPA induces ROS via the phospholipase C/PKC/NOX pathway (19,20). Hence, we hypothesized that ROS could specifically augment total TAZ levels.…”

Section: H 2 O 2 Elevates Total Protein Levels Of Taz and Increasesmentioning

confidence: 96%

Section: H 2 O 2 -Mediated Activation Of Taz Depends On S-glutathionymentioning

confidence: 99%

Cysteine S-Glutathionylation Promotes Stability and Activation of the Hippo Downstream Effector Transcriptional Co-activator with PDZ-binding Motif (TAZ)

Gandhirajan

Jain

Walla

et al. 2016

Journal of Biological Chemistry

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“…Lysophosphatidic acid (LPA), a bioactive lysophospholipid, is implicated in several physiological functions, including cell proliferation, migration, angiogenesis and lymphangiogenesis [5][6][7][8][9]. To date, six G protein-coupled receptors, including LPA 1~6 , were identified to mediate the cellular functions of LPA.…”

Section: Introductionmentioning

confidence: 99%

“…VEGF-C binds to VEGF receptor-3 (VEGFR-3) and activates the subsequent signaling events in lymphatic endothelial cells [13]. Moreover, we revealed that LPA-induced VEGF-C via generating reactive oxygen species (ROS) and lens epithelium-derived growth factor (LEDGF) [5,9]. Since PCa-releasing VEGF-C has been shown to mediate lymphatic metastasis [14], blocking LPA-mediated signaling might be a potential strategy to confine metastasis of PCa.…”

Section: Introductionmentioning

confidence: 99%

High Glucose Induces VEGF-C Expression via the LPA1/3-Akt-ROS-LEDGF Signaling Axis in Human Prostate Cancer PC-3 Cells

Huang¹,

Lin²,

Lin³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Hyperglycemia has been shown to increase the incidence and metastasis in various types of cancers. However, the correlation between hyperglycemia and lymphatic metastasis in prostate cancer (PCa) remains unclear. Our previous study demonstrated that lysophosphatidic acid (LPA) enhances vascular endothelial growth factor-C (VEGF-C) expression, a lymphangiogenic factor, through activating it receptors LPA_1/3 in prostate cancer (PCa) cells. Moreover, hyperglycemia up-regulates autotaxin (ATX) expression, a LPA-generating enzyme. Therefore, we propose that high glucose promotes VEGF-C expression through LPA signaling in PCa cells. Methods: Pharmacological inhibitors and siRNAs were utilized to investigate the molecular mechanism of high glucose-induced VEGF-C expression. Real-time PCR and Western blot were used to determine the mRNA and protein expressions, respectively. Cellular bioenergetics analysis was performed to determine the glycolysis levels. Results: We demonstrated that the expressions of VEGF-C, ATX, and calreticulin were increased upon high glucose treatments in PC-3 cells. Moreover, high glucose-induced VEGF-C expression was mediated through the LPA_1/3, PLC, Akt, ROS and LEDGF-dependent pathways. Additionally, high glucose enhanced the aerobic glycolysis via LPA_1/3. Conclusion: These results indicated that hyperglycemia leads to LPA synthesis, and subsequent promoting pathological consequence of PCa. These novel findings could potentially provide new strategies for PCa treatments.

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“…A variety of inflammatory factors, including interferon-γ, interleukin (IL)-4, IL-5, IL-6, IL-8 and IL-10, increase in the peripheral blood, indicating that myocardial infarction is a non-infectious immune inflammatory process (8,9). The immune inflammatory response has an important role in myocardial infarction (10,11). Numerous studies have focused on the effect of LPA on myocardial ischemia, but there are no reports on the immune regulatory effect of LPA on connexin 43 (Cx43) protein expression and arrhythmias (1,4,12).…”

Section: Introductionmentioning

confidence: 99%

Effect of lysophosphatidic acid on the immune inflammatory response and the connexin 43 protein in myocardial infarction

Zhang

Zhao

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Lysophosphatidic acid (LPA) is an intermediate product of membrane phospholipid metabolism. Recently, LPA has gained attention for its involvement in the pathological processes of certain cardiovascular diseases. The aim of the present study was to clarify the association between the effect of LPA and the immune inflammatory response, and to investigate the effects of LPA on the protein expression levels of connexin 43 during myocardial infarction. Surface electrocardiograms of myocardial infarction rats and isolated rat heart tissue samples were obtained in order to determine the effect of LPA on the incidence of arrhythmia in rats that exhibited changes in immune status. The results demonstrated that the incidence of arrhythmia decreased when the rat immune systems were suppressed, and the incidence of arrhythmia increased when the rat immune systems were enhanced. The concentration levels of tumor necrosis factor (TNF)-α were determined by ELISA, and the results demonstrated that LPA induced T lymphocyte synthesis and TNF-α release. Using a patch-clamp technique, LPA was shown to increase the current amplitude of the voltage-dependent potassium channels (K v ) and calcium-activated potassium channels (K Ca ) in Jurkat T cells. The protein expression of connexin 43 (Cx43) was determined by immunohistochemical staining. The results indicated that LPA caused the degradation of Cx43 and decreased the expression of Cx43. This effect was associated with the immune status of the rats. There was a further decrease in Cx43 expression in the rats of the immune-enhanced group. To the best of our knowledge, these results provide the first evidence that LPA causes arrhythmia through the regulation of immune inflammatory cells and the decrease of Cx43 protein expression. The present study provided an experimental basis for the treatment of arrhythmia and may guide clinical care. IntroductionAcute myocardial infarction (AMI) is a disease that severely affects the health and life quality of patients. Arrhythmia is a complication of myocardial infarction, which is one of the most severe cardiovascular diseases, and it is the predominant cause of myocardial infarction-associated mortality (1). Since patients with ischemic heart disease are particularly prone to arrhythmias, they are often admitted for arrhythmia monitoring (2). Lysophosphatidic acid (LPA), which is an intermediate product of membrane phospholipid metabolism, is a lipid mediator with various biological functions that are predominantly mediated by specific G protein-coupled receptors (3). As a water-soluble glycerol phospholipid with a simple structure, LPA is secreted from numerous cell types, including platelets, fibroblasts and ovarian cancer cells (4). The concentration of LPA in regional myocardial tissue and plasma increases during myocardial infarction, and it can also cause arrhythmia (5).During myocardial infarction, both the infarcted area and the non-infarcted area exhibit perivasculitis, and the infiltration of a large number of inflammator...

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Lysophosphatidic acid induces reactive oxygen species generation by activating protein kinase C in PC-3 human prostate cancer cells

Cited by 28 publications

References 31 publications

Cysteine S-Glutathionylation Promotes Stability and Activation of the Hippo Downstream Effector Transcriptional Co-activator with PDZ-binding Motif (TAZ)

Cysteine S-Glutathionylation Promotes Stability and Activation of the Hippo Downstream Effector Transcriptional Co-activator with PDZ-binding Motif (TAZ)

High Glucose Induces VEGF-C Expression via the LPA1/3-Akt-ROS-LEDGF Signaling Axis in Human Prostate Cancer PC-3 Cells

Effect of lysophosphatidic acid on the immune inflammatory response and the connexin 43 protein in myocardial infarction

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