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The dataset of methylglyoxal activating p38 and p44/42 pathway in osteoclast.

ABSTRACT: Diabetes mellitus (DM) is a kind of chronic metabolic disease that could be characterized by uncontrollable high blood glucose (hyperglycemia) over a prolonged period and diverse complications in various organs. These complications include activation of stress responses in bone such as oxidative stress and inflammation, which have been implicated in various bone diseases, including osteoporosis. Non-enzymatic glycation of proteins form and accumulate in patients under hyperglycemia condition. Methylglyoxal (MG) is a reactive advanced glycation end-product precursor. Abnormal high concentration of MG was in serum of diabetic patients. It was proven that MG induces various stress responses. This indicates that it might possibly the key metabolite leading to diabetes-associated bone loss. In this data report, using cell models, the underlying mechanism of methylglyoxal on osteoclast that may lead to bone loss was investigated. In cell cultures, RAW264.7, Macrophages, was treated with methylglyoxal and gene expressions of osteoclast bone biomarkers were investigated. Furthermore, the inhibitions of p38 and p44/42 activities were employed to investigate the osteoclast biomarkers CTSK, OSCAR, and TRACP5 gene expressions. These data implied that MG activated the p38 and p44/42, which was reported to regulate proliferation and differentiation of osteoclast. However, the decreasing MAPK though siRNA knockdown did not change expression of those target markers, TRACP5, OSCAR, and CTSK, in mRNA level. The effects of MG to other osteoclast markers through p38 and p44/42 would be worth to be investigated. For more insight please see Methylglyoxal Activates Osteoclasts through JNK Pathway leading to Osteoporosis.

SUBMITTER: Lee KM

PROVIDER: S-EPMC6811967 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesThe gap junction protein, connexin (Cx), plays an important role in maintaining cellular homeostasis and cell proliferation by allowing communication between adjacent cells. Therefore, this study has examined the effect of epidermal growth factor (EGF) on Cx43 and its relationship to proliferation of mouse embryonic stem cells.Materials and methodsExpressions of Cx43, mitogen-activated protein kinases (MAPKs) and cell cycle regulatory proteins were assessed by Western blot analysis. Cell proliferation was assayed with [(3)H]thymidine incorporation. Intercellular communication level was measured by a scrape loading/dye transfer method.ResultsThe results showed that EGF increased the level of Cx43 phosphorylation in a time- (> or =5 min) and dose- (> or =10 ng/mL) dependent manner. Indeed, EGF-induced increase in phospho-Cx43 level was significantly blocked by either AG 1478 or herbimycin A (tyrosine kinase inhibitors). EGF increased Ca(2+) influx and protein kinase C (PKC) translocation from the cytosolic compartment to the membrane compartment. Moreover, pre-treatment with BAPTA-AM (an intracellular Ca(2+) chelator), EGTA (an extracellular Ca(2+) chelator), bisindolylmaleimide I or staurosporine (PKC inhibitors) inhibited the EGF-induced phosphorylation of Cx43. EGF induced phosphorylation of p38 and p44/42 MAPKs, and this was blocked by SB 203580 (a p38 MAPK inhibitor) and PD 98059 (a p44/42 MAPK inhibitor), respectively. EGF or 18alpha-glycyrrhetinic acid (GA; a gap junction inhibitor) increased expression levels of the protooncogenes (c-fos, c-jun and c-myc), cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), CDK4 and p-Rb], [(3)H]thymidine incorporation and cell number, but decreased expression levels of the p21(WAF1/Cip1) and p27(Kip1), CDK inhibitory proteins. Transfection of Cx43 siRNA also increased the level of [(3)H]thymidine incorporation and cell number. EGF, 18alpha-GA or transfection of Cx43 siRNA increased 2-DG uptake and GLUT-1 protein expression.ConclusionsEGF-induced phosphorylation of Cx43, which was mediated by the Ca(2+)/PKC, p44/42 and p38 MAPKs pathways, partially contributed to regulation of mouse embryonic stem cell proliferation.

Project description:Angiotensin II (Ang II), acting via angiotensin type 1 receptors in the brain, activates the sympathetic nervous system in heart failure (HF). We reported recently that Ang II stimulates mitogen-activated protein kinase (MAPK) to upregulate brain angiotensin type 1 receptors in HF rats. In this study we tested the hypothesis that Ang II-activated MAPK signaling pathways contribute to sympathetic excitation in HF. Intracerebroventricular administration of PD98059 and UO126, 2 selective p44/42 MAPK inhibitors, induced significant decreases in mean arterial pressure, heart rate, and renal sympathetic nerve activity in HF rats, but had no effect on these variables in sham-operated rats. Pretreatment with losartan attenuated the effects of PD98059. Intracerebroventricular administration of the p38 MAPK inhibitor SB203580 and the c-Jun N-terminal kinase inhibitor SP600125 had no effect on mean arterial pressure, heart rate, or renal sympathetic nerve activity in HF. The phosphatidylinositol 3-kinase inhibitor LY294002 induced a small decrease in mean arterial pressure and heart rate but no change in renal sympathetic nerve activity. Immunofluorescent staining demonstrated increased p44/42 MAPK activity in neurons of the paraventricular nucleus of the hypothalamus of HF rats, colocalized with Fra-like activity (indicating chronic neuronal excitation). Intracerebroventricular PD98059 and UO126 reduced Fra-like activity in the paraventricular nucleus of the hypothalamus neurons in HF rats. In confirmatory acute studies, intracerebroventricular Ang II increased mean arterial pressure, heart rate, and renal sympathetic nerve activity in baroreceptor-denervated rats and Fra-like immunoreactivity in the paraventricular nucleus of the hypothalamus of neurally intact rats. Central administration of PD98059 markedly reduced these responses. These data demonstrate that intracellular p44/42 MAPK activity contributes to Ang II-induced neuronal excitation in the paraventricular nucleus of the hypothalamus and augmented sympathetic nerve activity in rats with HF.

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The dataset of methylglyoxal activating p38 and p44/42 pathway in osteoclast.

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