scholarly journals PRP4 Promotes Skin Cancer by Inhibiting Production of Melanin, Blocking Influx of Extracellular Calcium, and Remodeling Cell Actin Cytoskeleton

2021 ◽  
Vol 22 (13) ◽  
pp. 6992
Author(s):  
Muhammad Bilal Ahmed ◽  
Salman Ul Islam ◽  
Young Sup Lee
Keyword(s):  
Drug Resistance ◽  
Actin Cytoskeleton ◽  
Transient Receptor Potential ◽  
Epithelial Mesenchymal Transition ◽  
Receptor Potential ◽  
Extracellular Calcium ◽  
Melanin Biosynthesis ◽  
Mesenchymal Transition ◽  
B16f10 Cells ◽  
Transient Receptor

Pre-mRNA processing factor 4B (PRP4) has previously been shown to induce epithelial-mesenchymal transition (EMT) and drug resistance in cancer cell lines. As melanin plays an important photoprotective role in the risk of sun-induced skin cancers, we have investigated whether PRP4 can induce drug resistance and regulate melanin biosynthesis in a murine melanoma (B16F10) cell line. Cells were incubated with a crucial melanogenesis stimulator, alpha-melanocyte-stimulating hormone, followed by transfection with PRP4. This resulted in the inhibition of the production of melanin via the downregulation of adenylyl cyclase-cyclic adenosine 3’,5’-monophosphate (AC)–(cAMP)–tyrosinase synthesis signaling pathway. Inhibition of melanin production by PRP4 leads to the promotion of carcinogenesis and induced drug resistance in B16F10 cells. Additionally, PRP4 overexpression upregulated the expression of β-arrestin 1 and desensitized the extracellular calcium-sensing receptor (CaSR), which in turn, inhibited the influx of extracellular Ca2+ ions. The decreased influx of Ca2+ was confirmed by a decreased expression level of calmodulin. We have demonstrated that transient receptor potential cation channel subfamily C member 1 was involved in the influx of CaSR-induced Ca2+ via a decreasing level of its expression. Furthermore, PRP4 overexpression downregulated the expression of AC, decreased the synthesis of cAMP, and modulated the actin cytoskeleton by inhibiting the expression of Ras homolog family member A (RhoA). Our investigation suggests that PRP4 inhibits the production of melanin in B16F10 cells, blocks the influx of Ca2+ through desensitization of CaSR, and modulates the actin cytoskeleton through downregulating the AC–cAMP pathway; taken together, these observations collectively lead to the promotion of skin carcinogenesis.

scholarly journals Transient Receptor Potential Channel 6 Knockout Ameliorates Kidney Fibrosis by Inhibition of Epithelial–Mesenchymal Transition

2021 ◽  
Vol 8 ◽  
Author(s):  
Yanhong Zhang ◽  
Nina Yin ◽  
Anbang Sun ◽  
Qifang Wu ◽  
Wenzhu Hu ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Diseases ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Kidney Fibrosis ◽  
Mesenchymal Transition ◽  
Transient Receptor ◽  
End Stage ◽  
The Relationship

Kidney fibrosis is generally confirmed to have a significant role in chronic kidney disease, resulting in end-stage kidney failure. Epithelial–mesenchymal transition (EMT) is an important molecular mechanism contributing to fibrosis. Tubular epithelial cells (TEC), the major component of kidney parenchyma, are vulnerable to different types of injuries and are a significant source of myofibroblast by EMT. Furthermore, TRPC6 knockout plays an anti-fibrotic role in ameliorating kidney damage. However, the relationship between TRPC6 and EMT is unknown. In this study, TRPC6−/− and wild-type (WT) mice were subjected to a unilateral ureteric obstruction (UUO) operation. Primary TEC were treated with TGF-β1. Western blot and immunofluorescence data showed that fibrotic injuries alleviated with the inhibition of EMT in TRPC6−/− mice compared to WT mice. The activation of AKT-mTOR and ERK1/2 pathways was down-regulated in the TRPC6−/− mice, while the loss of Na+/K+-ATPase and APQ1 was partially recovered. We conclude that TRPC6 knockout may ameliorate kidney fibrosis by inhibition of EMT through down-regulating the AKT-mTOR and ERK1/2 pathways. This could contribute to the development of effective therapeutic strategies on chronic kidney diseases.

scholarly journals Role of Transient Receptor Potential Canonical Channel 6 (TRPC6) in Diabetic Kidney Disease by Regulating Podocyte Actin Cytoskeleton Rearrangement

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Qian Wang ◽  
Xuefei Tian ◽  
Yuyang Wang ◽  
Yan Wang ◽  
Jialin Li ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Actin Cytoskeleton ◽  
Diabetic Kidney Disease ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Diabetic Kidney ◽  
Transient Receptor Potential Canonical ◽  
Transient Receptor ◽  
Cytoskeleton Rearrangement

Podocyte injury is an important pathogenesis step causing proteinuric kidney diseases such as diabetic kidney disease (DKD). Actin cytoskeleton rearrangement in podocyte induced by multiple pathogenic factors is believed to be the key process resulting in glomerular injury. Many studies have recently shown that transient receptor potential canonical channel 6 (TRPC6) in podocyte plays a critical role in the development and progression of proteinuric kidney disease by regulating its actin cytoskeleton rearrangement. This review is aimed at summarizing the role of TRPC6 on DKD by regulating the podocyte actin cytoskeleton rearrangement, thereby help further broaden our views and understanding on the mechanism of DKD and provide a theoretic basis for exploring new therapeutic targets for DKD patients.

scholarly journals TRPV2 interacts with actin and reorganizes submembranous actin cytoskeleton

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Manoj Yadav ◽  
Chandan Goswami
Keyword(s):  
Actin Cytoskeleton ◽  
Transient Receptor Potential ◽  
Neuronal Damage ◽  
Ectopic Expression ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Filamentous Actin ◽  
Peripheral Neuron ◽  
Neurite Initiation ◽  
Transient Receptor

Abstract The understanding of molecules and their role in neurite initiation and/or extension is not only helpful to prevent different neurodegenerative diseases but also can be important in neuronal damage repair. In this work, we explored the role of transient receptor potential vanilloid 2 (TRPV2), a non-selective cation channel in the context of neurite functions. We confirm that functional TRPV2 is endogenously present in F11 cell line, a model system mimicking peripheral neuron. In F11 cells, TRPV2 localizes in specific subcellular regions enriched with filamentous actin, such as in growth cone, filopodia, lamellipodia and in neurites. TRPV2 regulates actin cytoskeleton and also interacts with soluble actin. Ectopic expression of TRPV2-GFP in F11 cell induces more primary and secondary neurites, confirming its role in neurite initiation, extension and branching events. TRPV2-mediated neuritogenesis is dependent on wildtype TRPV2 as cells expressing TRPV2 mutants reveal no neuritogenesis. These findings are relevant to understand the sprouting of new neurites, neuroregeneration and neuronal plasticity at the cellular, subcellular and molecular levels. Such understanding may have further implications in neurodegeneration and peripheral neuropathy.

Overexpression of TrpC5 promotes tumor metastasis via the HIF-1α–Twist signaling pathway in colon cancer

2017 ◽  
Vol 131 (19) ◽  
pp. 2439-2450 ◽  
Author(s):  
Zhen Chen ◽  
Yaodan Zhu ◽  
Yongfei Dong ◽  
Peng Zhang ◽  
Xiping Han ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Tumor Metastasis ◽  
Transient Receptor Potential ◽  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Mesenchymal Transition

In cancer cells, intracellular Ca2+ homeostasis is altered, and this is involved in tumor initiation, progression, and metastasis. However, little is known about the underlying mechanisms. Here, we report that transient receptor potential channel 5 (TrpC5), a receptor-activated non-selective Ca2+ channel, is correlated with tumor metastasis in colon cancer patients. Moreover, in colon cancer cells, overexpression of TrpC5 caused a robust rise in the concentration of ([Ca2+]i), decreased E-cadherin, and increased mesenchymal biomarker expression, then promoted cell migration, invasion, and proliferation. Interestingly, we found that TrpC5 mediated hypoxia-inducible factor 1α (HIF-1α) expression, activating Twist to promote the epithelial–mesenchymal transition (EMT). Notably, patients with high expression of TrpC5 displayed poorer overall and metastasis-free survival. Taken together, our findings demonstrate that TrpC5 induces the EMT through the HIF-1α–Twist signaling pathway to promote tumor metastasis in colon cancer.

scholarly journals Evodiamine Induces Transient Receptor Potential Vanilloid-1-Mediated Protective Autophagy in U87-MG Astrocytes

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ann-Jeng Liu ◽  
Sheng-Hao Wang ◽  
Sz-Ying Hou ◽  
Chien-Ju Lin ◽  
Wen-Ta Chiu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Extracellular Calcium ◽  
Motor Dysfunction ◽  
Transient Receptor Potential Vanilloid ◽  
Jnk Pathway ◽  
Mortality And Morbidity ◽  
Stroke Treatment ◽  
Transient Receptor

Cerebral ischemia is a leading cause of mortality and morbidity worldwide, which results in cognitive and motor dysfunction, neurodegenerative diseases, and death. Evodiamine (Evo) is extracted fromEvodia rutaecarpaBentham, a plant widely used in Chinese herbal medicine, which possesses variable biological abilities, such as anticancer, anti-inflammation, antiobesity, anti-Alzheimer’s disease, antimetastatic, antianoxic, and antinociceptive functions. But the effect of Evo on ischemic stroke is unclear. Increasing data suggest that activation of autophagy, an adaptive response to environmental stresses, could protect neurons from ischemia-induced cell death. In this study, we found that Evo induced autophagy in U87-MG astrocytes. A scavenger of extracellular calcium and an antagonist of transient receptor potential vanilloid-1 (TRPV-1) decreased the percentage of autophagy accompanied by an increase in apoptosis, suggesting that Evo may induce calcium-mediated protective autophagy resulting from an influx of extracellular calcium. The same phenomena were also confirmed by a small interfering RNA technique to knock down the expression of TRPV1. Finally, Evo-induced c-Jun N-terminal kinases (JNK) activation was reduced by a TRPV1 antagonist, indicating that Evo-induced autophagy may occur through a calcium/c-Jun N-terminal kinase (JNK) pathway. Collectively, Evo induced an influx of extracellular calcium, which led to JNK-mediated protective autophagy, and this provides a new option for ischemic stroke treatment.

scholarly journals TRPM7 residue S1269 mediates cAMP dependence of Ca2+ influx

2018 ◽  
Author(s):  
Jorrit Broertjes ◽  
Jeffrey Klarenbeek ◽  
Yasmin Habani ◽  
Michiel Langeslag ◽  
Kees Jalink
Keyword(s):  
Transient Receptor Potential ◽  
Cultured Cells ◽  
Mutational Analysis ◽  
Epithelial Mesenchymal Transition ◽  
Neuroblastoma Cells ◽  
Coiled Coil ◽  
Receptor Potential ◽  
Mesenchymal Transition ◽  
Transient Receptor Potential Melastatin ◽  
C Terminus

AbstractThe nonspecific divalent cation channel TRPM7 (transient receptor potential-melastatin-like 7) is involved in many Ca2+ and Mg2+-dependent cellular processes, including survival, proliferation and migration. TRPM7 expression predicts metastasis and recurrence in breast cancer and several other cancers. In cultured cells, it can induce an invasive phenotype by promoting Ca2+-mediated epithelial-mesenchymal transition. We previously showed that in neuroblastoma cells that overexpress TRPM7 moderately, stimulation with Ca2+-mobilizing agonists leads to a characteristic sustained influx of Ca2+. Here we report that sustained influx through TRPM7 is abruptly abrogated by elevating intracellular levels of cAMP. Using pharmacological inhibitors and overexpression studies we show that this blockage is mediated by the cAMP effector Protein Kinase A (PKA). Mutational analysis demonstrates that the Serine residue S1269, which is present proximal to the coiled-coil domain within the protein c-terminus, is responsible for sensitivity to cAMP.

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