scholarly journals Role of the AMPK/ACC Signaling Pathway in TRPP2-Mediated Head and Neck Cancer Cell Proliferation

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Kun Li ◽  
Lei Chen ◽  
Zhangying Lin ◽  
Junwei Zhu ◽  
Yang Fang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Feedback Mechanism ◽  
Initiation Factor ◽  
Expression Levels ◽  
Compound C

Transient receptor potential polycystic 2 (TRPP2) exerts vital roles in various types of cancer; however, its underlying mechanisms remain largely unknown. This study is aimed at investigating whether knockdown of TRPP2 affected the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling pathway and the proliferation of HN-4, cell line originating from human oral and hypopharyngeal squamous cell carcinoma. In addition, the interactions among AMPK/ACC, AMPK/protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α (eIF2α) and TRPP2/PERK/eIF2α signaling pathways, and their association with cell proliferation were also explored. The results showed that the relative expression levels of phosphorylated (p)-ACC, p-PERK, and p-eIF2α in HN-4 cells were significantly increased following treatment with 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) and significantly decreased in cells treated with compound C. Therefore, consistent with previous studies, the AMPK/ACC and AMPK/PERK/eIF2α signaling pathways were upregulated and downregulated following treatment with an AMPK agonist and inhibitor, respectively. Furthermore, TRPP2 knockdown decreased p-PERK and p-eIF2α expression levels and increased those of p-AMPK and p-ACC. Additionally, knockdown of TRPP2 increased HN-4 cell proliferation, while treatment with an AMPK inhibitor or agonist increased or inhibited TRPP2-specific siRNA-mediated cell proliferation, respectively. In conclusion, silencing of TRPP2 expression increased HN-4 cell proliferation via inhibiting the PERK/eIF2α signaling pathway, while the AMPK/ACC signaling pathway was possibly activated by a feedback mechanism to reduce enhanced cell proliferation.

Stress peptide PACAP engages multiple signaling pathways within the carotid body to initiate excitatory responses in respiratory and sympathetic chemosensory afferents

2013 ◽  
Vol 304 (12) ◽  
pp. R1070-R1084 ◽  
Author(s):  
Arijit Roy ◽  
Fatemeh Derakhshan ◽  
Richard J. A. Wilson
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Carotid Body ◽  
Stress Responses ◽  
Transient Receptor Potential ◽  
Channel Blocker ◽  
Receptor Potential ◽  
Peak Response ◽  
Transient Receptor ◽  
Multiple Signaling

Consistent with a critical role in respiratory and autonomic stress responses, the carotid bodies are strongly excited by pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide implicated in stress responses throughout the sympathetic nervous system. PACAP excites isolated carotid body glomus cells via activation of PAC1 receptors, with one study suggesting PAC1-induced excitation is due entirely to protein kinase A (PKA)-mediated inhibition of TASK channels. However, in other systems, PAC1 is known to be coupled to multiple intracellular signaling pathways, including PKA, phospholipase C (PLC), phospholipase D (PLD), and protein kinase C (PKC), that trigger multiple downstream effectors including increased Ca2+ mobilization, inhibition of various K+ channels, and activation of nonselective cation channels. This study tests if non-PKA/TASK channel signaling helps mediate the stimulatory effects of PACAP on the carotid body. Using an ex vivo arterially perfused rat carotid body preparation, we show that PACAP-38 stimulates carotid sinus nerve activity in a biphasic manner (peak response, falling to plateau). PKA blocker H-89 only reduced the plateau response (∼41%), whereas the TASK-1-like K+ channel blocker/transient receptor potential vanilloid 1 channel agonist anandamide only inhibited the peak response (∼48%), suggesting involvement of additional pathways. The PLD blocker CAY10594 significantly inhibited both peak and plateau responses. The PLC blocker U73122 decimated both peak and plateau responses. Brefeldin A, a blocker of Epac (cAMP-activated guanine exchange factor, reported to link Gs-coupled receptors with PLC/PLD), also reduced both phases of the response, as did blocking signaling downstream of PLC/PLD with the PKC inhibitors chelerythrine chloride and GF109203X. Suggesting the involvement of non-TASK ion channels in the effects of PACAP, the A-type K+ channel blocker 4-aminopyridine, and the putative transient receptor potential channel (TRPC)/T-type calcium channel blocker SKF96365 each significantly inhibited the peak and steady-state responses. These data suggest the stimulatory effect of PACAP-38 on carotid body sensory activity is mediated through multiple signaling pathways: the PLC-PKC pathways predominates, with TRPC and/or T-type channel activation and Kv channel inactivation; only partial involvement is attributable to PKA and PLD activation.

scholarly journals Activation of transient receptor potential vanilloid 4 protects articular cartilage against IL-1β-induced inflammatory responses by regulating the CaMKK/AMPK/NF-κB signaling pathway

2021 ◽  
Author(s):  
Kyosuke Hattori ◽  
Nobunori Takahashi ◽  
Kenya Terabe ◽  
Yoshifumi Ohashi ◽  
Kenji Kishimoto ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Protein Kinase ◽  
Transient Receptor Potential ◽  
Inflammatory Responses ◽  
Receptor Potential ◽  
Cartilage Tissue ◽  
Transient Receptor Potential Vanilloid ◽  
Compound C ◽  
Transient Receptor ◽  
Safranin O

Abstract Transient receptor potential vanilloid 4 (TRPV4) plays an important role in chondrocytes via Ca2+ signaling. However, its role in the progression of osteoarthritis is unclear. This study aimed to evaluate the effects of TRPV4 activation on articular cartilage and chondrocytes stimulated with interleukin (IL)-1β. Bovine and human articular chondrocytes were stimulated with various agents, including IL-1β, GSK1016790A (GSK101; a TRPV4 agonist), Compound C (an AMP-activated protein kinase (AMPK) inhibitor), and STO-609 (a calmodulin-dependent protein kinase kinase (CaMKK) inhibitor), and were processed for Western blot analysis and real-time PCR. The dimethylmethylene blue (DMMB) assay and Safranin O staining were also performed. GSK101 reversed the IL-1β-induced increase in expression of matrix metalloproteinase (MMP)-13 and decrease in expression of aggrecan. GSK101 also decreased proteoglycan release in the DMMB assay and retained Safranin O staining of articular cartilage tissue. Furthermore, GSK101 increased AMPK phosphorylation and decreased IL-1β-induced nuclear factor kappa B (NF-κB) phosphorylation. Compound C and STO-609 reversed the suppressive effects of GSK101 on NF-κB activation and MMP-13 expression. In conclusion, TRPV4 activation had chondroprotective effects on articular cartilage stimulated with IL-1β by activating CaMKK/AMPK and suppressing the NF-κB pathway. TRPV activators may offer a promising therapeutic option for preventing the progression of osteoarthritis.

scholarly journals Rutaecarpine Increases Nitric Oxide Synthesis via eNOS Phosphorylation by TRPV1-Dependent CaMKII and CaMKKβ/AMPK Signaling Pathway in Human Endothelial Cells

2021 ◽  
Vol 22 (17) ◽  
pp. 9407
Author(s):  
Gi Ho Lee ◽  
Chae Yeon Kim ◽  
Chuanfeng Zheng ◽  
Sun Woo Jin ◽  
Ji Yeon Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Ampk Signaling ◽  
Compound C ◽  
Enos Phosphorylation

Rutaecarpine (RUT) is a bioactive alkaloid isolated from the fruit of Evodia rutaecarpa that exerts a cellular protective effect. However, its protective effects on endothelial cells and its mechanism of action are still unclear. In this study, we demonstrated the effects of RUT on nitric oxide (NO) synthesis via endothelial nitric oxide synthase (eNOS) phosphorylation in endothelial cells and the underlying molecular mechanisms. RUT treatment promoted NO generation by increasing eNOS phosphorylation. Additionally, RUT induced an increase in intracellular Ca2+ concentration and phosphorylation of Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ), AMP-activated protein kinase (AMPK), and Ca2+/calmodulin-dependent kinase II (CaMKII). Inhibition of transient receptor potential vanilloid type 1 (TRPV1) attenuated RUT-induced intracellular Ca2+ concentration and phosphorylation of CaMKII, CaMKKβ, AMPK, and eNOS. Treatment with KN-62 (a CaMKII inhibitor), Compound C (an AMPK inhibitor), and STO-609 (a CaMKKβ inhibitor) suppressed RUT-induced eNOS phosphorylation and NO generation. Interestingly, RUT attenuated the expression of ICAM-1 and VCAM-1 induced by TNF-α and inhibited the inflammation-related NF-κB signaling pathway. Taken together, these results suggest that RUT promotes NO synthesis and eNOS phosphorylation via the Ca2+/CaMKII and CaM/CaMKKβ/AMPK signaling pathways through TRPV1. These findings provide evidence that RUT prevents endothelial dysfunction and benefit cardiovascular health.

scholarly journals Activation of transient receptor potential vanilloid 4 protects articular cartilage against inflammatory responses via CaMKK/AMPK/NF-κB signaling pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyosuke Hattori ◽  
Nobunori Takahashi ◽  
Kenya Terabe ◽  
Yoshifumi Ohashi ◽  
Kenji Kishimoto ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Protein Kinase ◽  
Transient Receptor Potential ◽  
Inflammatory Responses ◽  
Receptor Potential ◽  
Cartilage Tissue ◽  
Transient Receptor Potential Vanilloid ◽  
Compound C ◽  
Transient Receptor ◽  
Safranin O

AbstractTransient receptor potential vanilloid 4 (TRPV4) plays an important role in chondrocytes via Ca2+ signaling. However, its role in the progression of osteoarthritis is unclear. This study aimed to evaluate the effects of TRPV4 activation on articular cartilage and chondrocytes stimulated with interleukin (IL)-1β. Bovine and human articular chondrocytes were stimulated with various agents, including IL-1β, GSK1016790A (GSK101; a TRPV4 agonist), Compound C (an AMP-activated protein kinase (AMPK) inhibitor), and STO-609 (a calmodulin-dependent protein kinase kinase (CaMKK) inhibitor), and were processed for Western blot analysis and real-time PCR. The dimethylmethylene blue (DMMB) assay and Safranin O staining were also performed. GSK101 reversed the IL-1β-induced increase in expression of matrix metalloproteinase (MMP)-13 and decrease in expression of aggrecan. GSK101 also decreased proteoglycan release in the DMMB assay and retained Safranin O staining of articular cartilage tissue. Furthermore, GSK101 increased AMPK phosphorylation and decreased IL-1β-induced nuclear factor kappa B (NF-κB) phosphorylation. Compound C and STO-609 reversed the suppressive effects of GSK101 on NF-κB activation and MMP-13 expression. In conclusion, TRPV4 activation had chondroprotective effects on articular cartilage stimulated with IL-1β by activating CaMKK/AMPK and suppressing the NF-κB pathway. TRPV4 activators may offer a promising therapeutic option for preventing the progression of osteoarthritis.

scholarly journals The OsOXO2, OsOXO3 and OsOXO4 Positively Regulate Panicle Blast Resistance in Rice

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jingfang Dong ◽  
Lian Zhou ◽  
Aiqing Feng ◽  
Shaohong Zhang ◽  
Hua Fu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Blast Resistance ◽  
Aba Signaling ◽  
Leaf Blast ◽  
Expression Levels ◽  
Panicle Blast ◽  
Localization Analysis ◽  
Sa Signaling

Abstract Background Although panicle blast is more destructive to yield loss than leaf blast in rice, the cloned genes that function in panicle blast resistance are still very limited and the molecular mechanisms underlying panicle blast resistance remain largely unknown. Results In the present study, we have confirmed that the three Oxalate oxidase (OXO) genes, OsOXO2, OsOXO3 and OsOXO4 from a blast-resistant cultivar BC10 function in panicle blast resistance in rice. The expression of OsOXO2, OsOXO3 and OsOXO4 were induced by panicle blast inoculation. Subcellular localization analysis revealed that the three OXO proteins are all localized in the nucleus and cytoplasm. Simultaneous silencing of OsOXO2, OsOXO3 and OsOXO4 decreased rice resistance to panicle blast, whereas the OsOXO2, OsOXO3 and OsOXO4 overexpression rice plants individually showed enhanced panicle blast resistance. More H2O2 and higher expression levels of PR genes were observed in the overexpressing plants than in the control plants, while the silencing plants exhibited less H2O2 and lower expression levels of PR genes compared to the control plants. Moreover, phytohormone treatment and the phytohormone signaling related gene expression analysis showed that panicle blast resistance mediated by the three OXO genes was associated with the activation of JA and ABA signaling pathways but suppression of SA signaling pathway. Conclusion OsOXO2, OsOXO3 and OsOXO4 positively regulate panicle blast resistance in rice. The OXO genes could modulate the accumulation of H2O2 and expression levels of PR gene in plants. Moreover, the OXO genes mediated panicle blast resistance could be regulated by ABA, SA and JA, and may be associated with the activation of JA and ABA signaling pathways but suppression of the SA signaling pathway.

scholarly journals Transcriptome Profiling Reveals a Divergent Adaptive Response to Hyper- and Hypo-Salinity in the Yellow Drum, Nibea albiflora

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2201
Author(s):  
Xiang Zhao ◽  
Zhicheng Sun ◽  
Tianxiang Gao ◽  
Na Song
Keyword(s):  
Signaling Pathway ◽  
Salinity Stress ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Glutathione Metabolism ◽  
Pathway Enrichment Analysis ◽  
Northwest Pacific ◽  
Regulation Mechanism ◽  
Salinity Fluctuation ◽  
Nibea Albiflora

The yellow drum (Nibea albiflora) is an important marine economic fish that is widely distributed in the coastal waters of the Northwest Pacific. In order to understand the molecular regulatory mechanism of the yellow drum under salinity stress, in the present study, transcriptome analysis was performed under gradients with six salinities (10, 15, 20, 25, 30, and 35 psu). Compared to 25 psu, 907, 1109, 1309, 18, and 243 differentially expressed genes (DEGs) were obtained under 10, 15, 20, 30, and 35 psu salinities, respectively. The differential gene expression was further validated by quantitative real-time PCR (qPCR). The results of the tendency analysis showed that all DEGs of the yellow drum under salinity fluctuation were mainly divided into three expression trends. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the PI3K-Akt signaling pathway, Jak-STAT signaling pathway as well as the glutathione metabolism and steroid biosynthesis pathways may be the key pathways for the salinity adaptive regulation mechanism of the yellow drum. G protein-coupled receptors (GPCRs), the solute carrier family (SLC), the transient receptor potential cation channel subfamily V member 6 (TRPV6), isocitrate dehydrogenase (IDH1), and fructose-bisphosphate aldolase C-B (ALDOCB) may be the key genes in the response of the yellow drum to salinity stress. This study explored the transcriptional patterns of the yellow drum under salinity stress and provided fundamental information for the study of salinity adaptability in this species.

scholarly journals The Role of EGFR/PI3K/Akt/cyclinD1 Signaling Pathway in Acquired Middle Ear Cholesteatoma

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Liu ◽  
Hongmiao Ren ◽  
Jihao Ren ◽  
Tuanfang Yin ◽  
Bing Hu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
External Auditory Canal ◽  
Cell Cycle Progression ◽  
Critical Role ◽  
Immunohistochemical Method ◽  
Cycle Progression ◽  
Middle Ear Cholesteatoma

Cholesteatoma is a benign keratinizing and hyper proliferative squamous epithelial lesion of the temporal bone. Epidermal growth factor (EGF) is one of the most important cytokines which has been shown to play a critical role in cholesteatoma. In this investigation, we studied the effects of EGF on the proliferation of keratinocytes and EGF-mediated signaling pathways underlying the pathogenesis of cholesteatoma. We examined the expressions of phosphorylated EGF receptor (p-EGFR), phosphorylated Akt (p-Akt), cyclinD1, and proliferating cell nuclear antigen (PCNA) in 40 cholesteatoma samples and 20 samples of normal external auditory canal (EAC) epithelium by immunohistochemical method. Furthermore,in vitrostudies were performed to investigate EGF-induced downstream signaling pathways in primary external auditory canal keratinocytes (EACKs). The expressions of p-EGFR, p-Akt, cyclinD1, and PCNA in cholesteatoma epithelium were significantly increased when compared with those of control subjects. We also demonstrated that EGF led to the activation of the EGFR/PI3K/Akt/cyclinD1 signaling pathway, which played a critical role in EGF-induced cell proliferation and cell cycle progression of EACKs. Both EGFR inhibitor AG1478 and PI3K inhibitor wortmannin inhibited the EGF-induced EGFR/PI3K/Akt/cyclinD1 signaling pathway concomitantly with inhibition of cell proliferation and cell cycle progression of EACKs. Taken together, our data suggest that the EGFR/PI3K/Akt/cyclinD1 signaling pathway is active in cholesteatoma and may play a crucial role in cholesteatoma epithelial hyper-proliferation. This study will facilitate the development of potential therapeutic targets for intratympanic drug therapy for cholesteatoma.

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