Mechanisms shaping the role of ERK1/2 in cellular sene scence (Review)

Zou, Junrong; Lei, Tingting; Guo, Pei; Yu, Jigui; Xu, Qiuliang; Luo, Yunfei; Ke, Rong; Huang, Deqiang

doi:10.3892/mmr.2018.9712

Cited by 69 publications

(66 citation statements)

References 134 publications

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“…The nuclear regulation of ERK signalling with other phosphorylated proteins in the cell is very important to regulate the normal function of cells such as the cell cycle, cell proliferation and cell development. [ 49,50 ] Also, researchers expressed there was a possibility that generated ROS and RNS/NO in tumour cells regulate MMP9 expression and/or activation. [ 51–53 ] Flavonoids/flavones are direct scavengers of ROS and RNS.…”

Section: Discussionmentioning

confidence: 99%

A trimethoxy flavonoid isolated from stem extract of Tabebuia chrysantha suppresses angiogenesis in angiosarcoma

Panda

Panigrahy

Prasanth

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives This research aimed to evaluate the antiangiogenic activity of isolated flavonoid 4a,5,8,8a-tetrahydro-5-hydroxy-3,7,8-trimethoxy-2-(3,4-dimethoxyphenyl) chromen-4-one (TMF) from Tabebuia chrysantha. STAT3-MMP9 signalling is a signal transduction mechanism that promotes angiogenesis in various cancers. Methods The tumour xenografting chicken embryo chorioallantoic membrane (CAM) model-based ex vivo assay was used to evaluate the activity of TMF. The Western blot, densitometric analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to evaluate the activity of the MMP9. Zebrafish embryos were used to evaluate embryotoxicity, and in vitro free radical scavenging activity of flavonoid was also elucidated. Key findings This research assessed the high level of STAT3, p-ERK, VEGF-R and MMP9 in the tissue extract of the control group, and also, the suppression of angiogenesis in the treatment groups was due to scavenged ROS and RNS, dephosphorylation of STAT3 and ERK, and suppression of MMP9 gene expression. Conclusion The isolated flavonoid named TMF from T. chrysantha functions as specific regulators of target proteins of angiosarcoma. The STAT3-MMP9 signalling may be used as an effective prognostic marker of angiosarcoma.

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Section: Discussionmentioning

confidence: 99%

A trimethoxy flavonoid isolated from stem extract of Tabebuia chrysantha suppresses angiogenesis in angiosarcoma

Panda

Panigrahy

Prasanth

et al. 2020

Journal of Pharmacy and Pharmacology

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“…Moreover, ERK1/2 is a major member of Mitogen-activated protein kinases (MAPKs) family, which are ubiquitous eukaryotic signal transduction enzymes that stimulate the pathways related to intracellular gene expression and acting kinases. Therefore, ERK1/2 mediates extracellular signals to the nucleus for the regulation of cell cycle and cell proliferation 40,41 . Increasing evidence shows that SGK1 is a member of the CALMP-dependent protein kinase A, cGMP-dependent kinase G, and phospholipid-dependent protein kinase C (AGC) family of serine or threonine protein kinases and serves as a downstream regulator in the PI3K pathway.…”

Section: Discussionmentioning

confidence: 99%

Novel insights into molecular mechanisms of Pseudourostyla cristata encystment using comparative transcriptomics

Pan

Niu

Bhatti

et al. 2019

Sci Rep

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The encystment of many ciliates is an advanced survival strategy against adversity and the most important reason for ciliates existence worldwide. However, the molecular mechanism for the encystment of free-living ciliates is poorly understood. Here, we performed comparative transcriptomic analysis of dormant cysts and trophonts from Pseudourostyla cristata using transcriptomics, qRT-PCR and bioinformatic techniques. We identified 2565 differentially expressed unigenes between the dormant cysts and the trophonts. The total number of differentially expressed genes in GO database was 1752. The differential unigenes noted to the GO terms were 1993. These differential categories were mainly related to polyamine transport, pectin decomposition, cytoplasmic translation, ribosome, respiratory chain, ribosome structure, ion channel activity, and RNA ligation. A total of 224 different pathways were mapped. Among them, 184 pathways were upregulated, while 162 were downregulated. Further investigation showed that the calcium and AMPK signaling pathway had important induction effects on the encystment. In addition, FOXO and ubiquitin-mediated proteolysis signaling pathway jointly regulated the encystment. Based on these findings, we propose a hypothetical signaling network that regulates Pseudourostyla cristata encystment. Overall, these results provide deeper insights into the molecular mechanisms of ciliates encystment and adaptation to adverse environments.of Strepkiella histriomuscorum has been studied in the encystment and trophont stages through biochip technology, which suggested that cyst formation is associated with Ribosomal L7, Ribosomal acidic P2, Cathepsin B, Cathepsin H, Ubiquitin, Ca 2+ -ATPase and Actin1 7 . Other studies investigated the differential proteins of the cysts and the trophonts from Pseudourostyla cristata (P. cristata) using shotgun LC-MS/MS, finding the association of fibrillarin-like rRNA methylase, methylmalonyl-coenzyme mutase, ADP ribosylation factor, Rab12, MAPK-related kinase and KR multi-domain proteins with cyst formation 8 . However, the reports of systematically studying the genes and signaling pathways involved in the formation of ciliate cysts at the molecular level are rare 8 . In this study, we have investigated the molecular mechanism underlying the cyst formation in ciliates using comparative transcriptomic analysis, quantitative real-time PCR (qRT-PCR) and bioinformatic techniques. Furthermore, we have focused on the analysis of several important signaling pathways related to the encystment. Therefore, we have proposed a hypothetical network that regulates Pseudourostyla cristata encystment. Our study generates novel insights into the molecular mechanisms of the cyst formation in free-living ciliates.www.nature.com/scientificreports www.nature.com/scientificreports/ dormant cysts of P. cristata (Fig. 4). Validation of results by transcriptome sequencing showed that mRNA outcomes were consistent with the transcriptomic data of trophonts and dormant cysts in P. cristata (Fig. 4).

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“…Erks are also known to activate many transcription factors (e.g. c-myc, c-Fos, AP-1, and Elk1) responsible for regulation of various target genes [35]. It has been found that Ang II stimulates Erk1/2 activation and Nox4-derived ROS production in glomerular mesangial cells [36].…”

Section: Plos Onementioning

confidence: 99%

Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway

Che

Gao

et al. 2020

PLoS ONE

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Angiotensin II (Ang II) is a key contributor to glomerular disease by predominantly resulting in podocyte injury, whereas the underlying molecular mechanisms has not been fully understood. This study aimed to investigate if and how ADP-ribosylation factor 6 (Arf6), a small GTP-binding protein, involves Ang II-induced cellular injury in cultured human podocytes. Cellular injury was evaluated with caspase 3 activity, reactive oxygen species (ROS) level and TUNEL assay. Arf6 activity was measured using an Arf6-GTP Pull-Down Assay. Ang II significantly enhanced Arf6 expressions accompanied by increase of Arf6-GTP. The TUNEL-positive cells as well as activated caspase 3, NADPH oxidase 4 protein (Nox4) and ROS levels were dramatically increased in Ang II-treated podocytes, which was prevented by secinH3, an Arf6 activity inhibitor. Induction of ROS by Ang II was inhibited in podocytes with Nox4 knockdown. Ang II-induced elevation of Nox4 and ROS was prevented by Arf6 knockdown. Phpspho-Erk1/2 Thr202/Tyr204 levels were upregulated remarkably following Ang II treatment, and Erk inhibitor LY3214996 significantly downregulated Nox4 expression. In addition, Ang II decreased CD2AP expression. Overexpression of CD2AP prevented Ang IIinduced upregulation of Arf6-GTP. Our data demonstrated that Ang II promotes ROS production and podocytes injury through activation of Arf6-Erk1/2-Nox4 signaling. We also provided evidence that Ang II activates Arf6 by degradation of CD2AP.

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Mechanisms shaping the role of ERK1/2 in cellular sene scence (Review)

Cited by 69 publications

References 134 publications

A trimethoxy flavonoid isolated from stem extract of Tabebuia chrysantha suppresses angiogenesis in angiosarcoma

A trimethoxy flavonoid isolated from stem extract of Tabebuia chrysantha suppresses angiogenesis in angiosarcoma

Novel insights into molecular mechanisms of Pseudourostyla cristata encystment using comparative transcriptomics

Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway

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