Atrial Natriuretic Peptide Effects on Intracellular pH Changes and ROS Production in HEPG2 Cells: Role of p38 MAPK and Phospholipase D

Baldini, P.; Vito, Paolo De; Vismara, D; Bagni, Claudia; Zalfa, Francesca; Minieri, Marilena; Nardo, Paolo Di

doi:10.1159/000083640

Cited by 23 publications

(7 citation statements)

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“…Therefore, ROS, cAMP, PKC and NHE may be involved in the processes of protein carbonylation and actin glutathionylation after exposure to Cd in haemocytes of mussels. This statement is in accordance with previously published studies, indicating that ROS production could be induced by a NHE-dependent pathway (Rothstein et al, 2002;Sand et al, 2003;Baldini et al, 2005). However, further research is needed in order for this to be verified.…”

Section: Discussionsupporting

confidence: 93%

The role of signalling molecules on actin glutathionylation and protein carbonylation induced by cadmium in haemocytes of musselMytilus galloprovincialis(Lmk)

Dailianis

Patetsini

Kaloyianni

2009

Journal of Experimental Biology

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SUMMARYThis study investigated the role of Na + /H + exchanger (NHE) and signalling molecules, such as cAMP, PKC, PI 3-kinase, and immune defence enzymes, NADPH oxidase and nitric oxide synthase, in the induction of protein glutathionylation and carbonylation in cadmium-treated haemocytes of mussel Mytilus galloprovincialis. Glutathionylation was detected by western blot analysis and showed actin as its main target. A significant increase of both actin glutathionylation and protein carbonylation, were observed in haemocytes exposed to micromolar concentration of cadmium chloride (5moll -1 ). Cadmium seems to cause actin polymerization that may lead to its increased glutathionylation, probably to protect it from cadmium-induced oxidative stress. It is therefore possible that polymerization of actin plays a signalling role in the induction of both glutathionylation and carbonylation processes. NHE seems to play a regulatory role in the induction of oxidative damage and actin glutathionylation, since its inhibition by 2moll -1 cariporide, significantly diminished cadmium effects in each case. Similarly, attenuation of cadmium effects were observed in cells pre-treated with either 11moll -1 GF-109203X, a potent inhibitor of PKC, 50nmoll -1 wortmannin, an inhibitor of PI 3-kinase, 0.01mmoll -1 forskolin, an adenylyl cyclase activator, 10moll -1 DPI, a NADPH oxidase inhibitor, or 10moll -1 L-NAME, a nitric oxide synthase inhibitor, suggesting a possible role of PKC, PI 3-kinase and cAMP, as well as NADPH oxidase and nitric oxide synthase in the enhancement of cadmium effects on both actin glutathionylation and protein carbonylation.

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Section: Discussionsupporting

confidence: 93%

The role of signalling molecules on actin glutathionylation and protein carbonylation induced by cadmium in haemocytes of musselMytilus galloprovincialis(Lmk)

Dailianis

Patetsini

Kaloyianni

2009

Journal of Experimental Biology

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“…4A). The production of reactive oxygen species (ROS) has been reported to increase when pHi was decreased, suggesting that ROS is also a major stress to cells under acidic environments (Baldini et al, 2005). Both the transcription and activity of MnSOD were significantly increased in siNone at pHe 6.3, while the suppression of MnSOD activity and significant cytoplasm acidification was observed in siCTIB at pHe 6.3 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Requirement of an IκB‐β COOH terminal region protein for acidic‐adaptation in CHO cells

Lao

Fukamachi

Saito

et al. 2005

Journal Cellular Physiology

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We previously reported that an IkappaB-beta COOH terminal region protein (designated CTIB) was essential for the proliferation of CHO cells under acidic stress (Lao et al., 2005. J Cell Physiol 203(1):186-192). In order to investigate the mechanisms underlying the requirement of CTIB for acidic adaptation, CTIB was silenced with an RNAi technique in CHO cells. CTIB silencing resulted in those cells completely failing to proliferate and maintain intracellular pH (pHi) homeostasis at an extracellular pH (pHe) of 6.3. An increased activation of p38 MAP kinase was induced by CTIB silencing at the low pH value. CTIB was only present in the cytoplasm and co-immunoprecipitation of the cytoplasmic fraction revealed that the loss of CTIB led to a loss of p65 in the immunoprecipitate complex. CTIB silencing reduced both the decrease in p65 and the increase in p50 in the nucleus when the cells were incubated at pHe 6.3. In cells with CTIB silenced, the transcriptions of p65, p105, and IL1-beta were suppressed, and decreases in both the transcription and activity of MnSOD were observed at pHe 6.3. Suppression of these genes suggested a suppressed NF-kappaB activity since p105, IL1-beta, and MnSOD were target genes of NF-kappaB. Our data demonstrated that CTIB functioned to prevent the over-accumulation of p65 in the nucleus, ensuring the appropriate composition of the NF-kappaB complex in the nucleus to respond to stimuli under acidic conditions.

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“…In the 2005, Baldini and collaborators demonstrated that in HepG2 hepatoblastoma cells, ANP induced intracellular acidification by decreasing NHE-1 expression and activity [57]. These Authors suggested that the ANP effect on pH i was mediated by NPR-C receptors.…”

Section: Innovative Targets For Antitumor Activity Of Anpmentioning

confidence: 99%

Atrial Natriuretic Peptide: A Magic Bullet for Cancer Therapy Targeting Wnt Signaling and Cellular pH Regulators

Serafino¹,

Pierimarchi

2014

CMC

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Atrial natriuretic peptide (ANP) is a cardiac hormone playing a crucial role in cardiovascular homeostasis mainly through blood volume and pressure regulation. In the last years, the new property ascribed to ANP of inhibiting tumor growth both in vitro and in vivo has made this peptide an attractive candidate for anticancer therapy. The molecular mechanism underlying the anti-proliferative effect of ANP has been mainly related to its interaction with the specific receptors NPRs, through which this natriuretic hormone inhibits some metabolic targets critical for cancer development, including the Ras-MEK1⁄2-ERK1⁄2 kinase cascade, functioning as a multikinase inhibitor. In this review we summarize the current knowledge on this topic, focusing on our recent data demonstrating that the antitumor activity of this natriuretic hormone is also mediated by a concomitant effect on the Wnt/β-catenin pathway and on the pH regulation ability of cancer cells, through a Frizzled-related mechanism. This peculiarity of simultaneously targeting two processes crucial for neoplastic transformation and solid tumor survival reinforces the utility of ANP for the development of both preventive and therapeutic strategies.

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Atrial Natriuretic Peptide Effects on Intracellular pH Changes and ROS Production in HEPG2 Cells: Role of p38 MAPK and Phospholipase D

Cited by 23 publications

References 50 publications

The role of signalling molecules on actin glutathionylation and protein carbonylation induced by cadmium in haemocytes of musselMytilus galloprovincialis(Lmk)

The role of signalling molecules on actin glutathionylation and protein carbonylation induced by cadmium in haemocytes of musselMytilus galloprovincialis(Lmk)

Requirement of an IκB‐β COOH terminal region protein for acidic‐adaptation in CHO cells

Atrial Natriuretic Peptide: A Magic Bullet for Cancer Therapy Targeting Wnt Signaling and Cellular pH Regulators

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