scholarly journals Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 525 ◽  
Author(s):  
Maria Beatrice Morelli ◽  
Consuelo Amantini ◽  
Daniele Tomassoni ◽  
Massimo Nabissi ◽  
Antonella Arcella ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
U251 Cell ◽  
Mediated Effects ◽  
Kaplan Meier ◽  
Negative Prognostic Factor ◽  
Carbonyl Cyanide ◽  
Transient Receptor

A link between mucolipin channels and tumors has been recently suggested. Herein, we aim to investigate the transient receptor potential mucolipin (TRPML)-1 relevance in glioblastoma. The expression of this channel was evaluated via qRT-PCR and immunohistochemistry in biopsies from 66 glioblastoma patients and two human glioblastoma cell lines and compared to normal human brain, astrocytes, and epileptic tissues. The subcellular distribution of TRPML-1 was examined via confocal microscopy in the glioma cell lines. Then, to assess the role of TRPML-1, cell viability assays have been conducted in T98 and U251 cell lines treated with the specific TRPML-1 agonist, MK6-83. We found that MK6-83 reduced cell viability and induced caspase-3-dependent apoptosis. Indeed, the TRPML-1 silencing or the blockage of TRPML-1 dependent [Ca2+]i release abrogated these effects. In addition, exposure of glioma cells to the reactive oxygen species (ROS) inducer, carbonyl cyanide m-chlorophenylhydrazone (CCCP), stimulated a TRPML-1-dependent autophagic cell death, as demonstrated by the ability of the autophagic inhibitor bafilomycin A, the TRPML-1 inhibitor sphingomyelin, and the TRPML-1 silencing to completely inhibit the CCCP-mediated effects. To test a possible correlation with patient’s survival, Kaplan–Meier, univariate, and multivariate analysis have been performed. Data showed that the loss/reduction of TRPML-1 mRNA expression strongly correlates with short survival in glioblastoma (GBM) patients, suggesting that the reduction of TRPML-1 expression represents a negative prognostic factor in GBM patients.

scholarly journals Mechanism for Regulation of Melanoma Cell Death via Activation of Thermo-TRPV4 and TRPV2

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jiaojiao Zheng ◽  
Fangyuan Liu ◽  
Sha Du ◽  
Mei Li ◽  
Tian Wu ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Melanoma Cells ◽  
Human Malignant Melanoma ◽  
Transient Receptor ◽  
A375 Cells

Background. Thermo-TRPs (temperature-sensitive transient receptor potential channels) belong to the TRP (transient receptor potential) channel superfamily. Emerging evidence implied that thermo-TRPs have been involved in regulation of cell fate in certain tumors. However, their distribution profiles and roles in melanoma remain incompletely understood. Methods. Western blot and digital PCR approaches were performed to identify the distribution profiles of six thermo-TRPs. MTT assessment was employed to detect cell viability. Flow cytometry was applied to test cell cycle and apoptosis. Calcium imaging was used to determine the function of channels. Five cell lines, including one normal human primary epidermal melanocytes and two human malignant melanoma (A375, G361) and two human metastatic melanoma (A2058, SK-MEL-3) cell lines, were chosen for this research. Results. In the present study, six thermo-TRPs including TRPV1/2/3/4, TRPA1, and TRPM8 were examined in human primary melanocytes and melanoma cells. We found that TRPV2/4, TRPA1, and TRPM8 exhibited ectopic distribution both in melanocytes and melanoma cells. Moreover, activation of TRPV2 and TRPV4 could lead to the decline of cell viability for melanoma A2058 and A375 cells. Subsequently, activation of TRPV2 by 2-APB (IC50 = 150 μM) induced cell necrosis in A2058 cells, while activation of TRPV4 by GSK1016790A (IC50 = 10 nM) enhanced apoptosis of A375 cells. Furthermore, TRPV4 mediated cell apoptosis of melanoma via phosphorylation of AKT and was involved in calcium regulation. Conclusion. Overall, our studies revealed that TRPV4 and TRPV2 mediated melanoma cell death via channel activation and characterized the mechanism of functional TRPV4 ion channel in regulating AKT pathway driven antitumor process. Thus, they may serve as potential biomarkers for the prognosis and are targeted for the therapeutic use in human melanoma.

scholarly journals Antioncogenic Effects of Transient Receptor Potential Vanilloid 1 in the Progression of Transitional Urothelial Cancer of Human Bladder

ISRN Urology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Giorgio Santoni ◽  
Sara Caprodossi ◽  
Valerio Farfariello ◽  
Sonia Liberati ◽  
Angela Gismondi ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Transient Receptor Potential ◽  
Transitional Cell ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Signaling Proteins ◽  
Human Bladder ◽  
Negative Prognostic Factor ◽  
Transient Receptor

The progression of normal cells to a tumorigenic and metastatic state involves the accumulation of mutations in multiple key signaling proteins, encoded by oncogenes and tumor suppressor genes. Recently, members of the TRP channel family have been included in the oncogenic and tumor suppressor protein family. TRPM1, TRPM8, and TRPV6 are considered to be tumor suppressors and oncogenes in localized melanoma and prostate cancer, respectively. Herein, we focus our attention on the antioncogenic properties of TRPV1. Changes in TRPV1 expression occur during the development of transitional cell carcinoma (TCC) of human bladder. A progressive decrease in TRPV1 expression as the TCC stage increases triggers the development of a more aggressive gene phenotype and invasiveness. Finally, downregulation of TRPV1 represents a negative prognostic factor in TCC patients. The knowledge of the mechanism controlling TRPV1 expression might improve the diagnosis and new therapeutic strategies in bladder cancer.

scholarly journals Expression of multiple Transient Receptor Potential channel genes in murine 3T3-L1 cell lines and adipose tissue

2013 ◽  
Vol 65 (3) ◽  
pp. 751-755 ◽  
Author(s):  
Mahendra Bishnoi ◽  
Kanthi Kiran Kondepudi ◽  
Aakriti Gupta ◽  
Aniket Karmase ◽  
Ravneet K. Boparai
Keyword(s):  
Adipose Tissue ◽  
Cell Lines ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Transient Receptor

scholarly journals Renal Tubular TRPA1 as a Risk Factor for Recovery of Renal Function from Acute Tubular Necrosis

2019 ◽  
Vol 8 (12) ◽  
pp. 2187 ◽  
Author(s):  
Chung-Kuan Wu ◽  
Chia-Lin Wu ◽  
Tzu-Cheng Su ◽  
Yu Ru Kou ◽  
Chew-Teng Kor ◽  
...  
Keyword(s):  
Renal Function ◽  
Acute Tubular Necrosis ◽  
Transient Receptor Potential ◽  
Kidney Injury ◽  
Receptor Potential ◽  
Total Recovery ◽  
Tubular Necrosis ◽  
Kaplan Meier ◽  
Transient Receptor ◽  
Renal Tubular

Background: Transient receptor potential ankyrin 1 (TRPA1), a redox-sensing Ca2+-influx channel, serves as a gatekeeper for inflammation. However, the role of TRPA1 in kidney injury remains elusive. Methods: The retrospective cohort study recruited 46 adult patients with acute kidney injury (AKI) and biopsy-proven acute tubular necrosis (ATN) and followed them up for more than three months. The subjects were divided into high- and low-renal-tubular-TRPA1-expression groups for the comparison of the total recovery of renal function and mortality within three months. The significance of TRPA1 in patient prognosis was evaluated using Kaplan–Meier curves and logistic regression analysis. Results: Of the 46 adult AKI patients with ATN, 12 totally recovered renal function. The expression level of tubular TRPA1 was detected by quantitative analysis of the immunohistochemistry of biopsy specimens from ATN patients. The AKI patients with high tubular TRPA1 expression showed a high incidence of nontotal renal function recovery than those with low tubular TRPA1 expression (OR = 7.14; 95%CI 1.35–37.75; p = 0.02). High TRPA1 expression was independently associated with nontotal recovery of renal function (adjusted OR = 6.86; 95%CI 1.26–37.27; p = 0.03). Conclusion: High tubular TRPA1 expression was associated with the nontotal recovery of renal function. Further mechanistic studies are warranted.

Regulation of TRP channel TRPM2 by the tyrosine phosphatase PTPL1

2007 ◽  
Vol 292 (5) ◽  
pp. C1746-C1758 ◽  
Author(s):  
Wenyi Zhang ◽  
Qin Tong ◽  
Kathleen Conrad ◽  
Jocelyn Wozney ◽  
Joseph Y. Cheung ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Tyrosine Phosphorylation ◽  
Transient Receptor Potential ◽  
Kinase Inhibitors ◽  
Tyrosine Phosphatase ◽  
Pdz Domain ◽  
Receptor Potential ◽  
Amyloid Peptide ◽  
Transient Receptor

TRPM2, a member of the transient receptor potential (TRP) superfamily, is a Ca2+-permeable channel, which mediates susceptibility to cell death following activation by oxidative stress, TNFα, or β-amyloid peptide. We determined that TRPM2 is rapidly tyrosine phosphorylated after stimulation with H2O2or TNFα. Inhibition of tyrosine phosphorylation with the tyrosine kinase inhibitors genistein or PP2 significantly reduced the increase in [Ca2+]iobserved after H2O2or TNFα treatment in TRPM2-expressing cells, suggesting that phosphorylation is important in TRPM2 activation. Utilizing a TransSignal PDZ domain array blot to identify proteins which interact with TRPM2, we identified PTPL1 as a potential binding protein. PTPL1 is a widely expressed tyrosine phosphatase, which has a role in cell survival and tumorigenesis. Immunoprecipitation and glutathione- S-transferase pull-down assays confirmed that TRPM2 and PTPL1 interact. To examine the ability of PTPL1 to modulate phosphorylation or activation of TRPM2, PTPL1 was coexpressed with TRPM2 in human embryonic kidney-293T cells. This resulted in significantly reduced TRPM2 tyrosine phosphorylation, and inhibited the rise in [Ca2+]iand the loss of cell viability, which follow H2O2or TNFα treatment. Consistent with these findings, reduction in endogenous PTPL1 expression with small interfering RNA resulted in increased TRPM2 tyrosine phosphorylation, a significantly greater rise in [Ca2+]ifollowing H2O2treatment, and enhanced susceptibility to H2O2-induced cell death. Endogenous TRPM2 and PTPL1 was associated in U937-ecoR cells, confirming the physiological relevance of this interaction. These data demonstrate that tyrosine phosphorylation of TRPM2 is important in its activation and function and that inhibition of TRPM2 tyrosine phosphorylation reduces Ca2+influx and protects cell viability. They also suggest that modulation of TRPM2 tyrosine phosphorylation is a mechanism through which PTPL1 may mediate resistance to cell death.

Do Fasudil and Y-27632 affect the level of transient receptor potential (TRP) gene expressions in breast cancer cell lines?

Tumor Biology ◽  
2014 ◽  
Vol 35 (8) ◽  
pp. 8033-8041 ◽  
Author(s):  
Bulent Gogebakan ◽  
Recep Bayraktar ◽  
Ali Suner ◽  
Ozan Balakan ◽  
Mustafa Ulasli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Gene Expressions ◽  
Transient Receptor

scholarly journals −254C>G SNP in the TRPC6 Gene Promoter Influences Its Expression via Interaction with the NF-κB Subunit RELA in Steroid-Resistant Nephrotic Syndrome Children

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Xinyu Kuang ◽  
Qian Zhou ◽  
Zhuying Li ◽  
Yujie Hu ◽  
Yulin Kang ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Cell Lines ◽  
Transient Receptor Potential ◽  
Gene Promoter ◽  
Receptor Potential ◽  
Pcr Analysis ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Mutant Sequence ◽  
Transient Receptor

This study is aimed at exploring the mechanism by which the −254C>G single nucleotide polymorphism (SNP) on the transient receptor potential cation channel 6 (TRPC6) gene promoter could increase its activation in steroid-resistant nephrotic syndrome children of China. Plasmids containing the TRPC6 promoter region (with the −254C or G allele) were constructed and then transfected into human embryonic kidney (HEK) 293T cells and human podocytes. Luciferase assays were used to test the promoter activity in both cell lines with or without tumor necrosis factor-α (TNF-α) treatment, and chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) analysis was used to verify the transcription factor that could bind to this mutant sequence. Luciferase results indicate that the activity of the mutant promoter was greater than that of the normal promoter of the TRPC6 gene in both cell lines. We further predicted and verified that this variation was mediated by the nuclear factor kappa B (NF-κB) subunit RELA, and TNF-α significantly enhanced the transcription activity of TRPC6 with the −254G allele. In conclusion, the −254C>G SNP is a gain-of-function variation of the TRPC6 gene, and it is also an early and effective factor for predicting steroid-resistant nephrotic syndrome (SRNS) in Chinese children.

scholarly journals The TRPA1 Channel Amplifies the Oxidative Stress Signal in Melanoma

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3131
Author(s):  
Francesco De Logu ◽  
Daniel Souza Monteiro de Araujo ◽  
Filippo Ugolini ◽  
Luigi Francesco Iannone ◽  
Margherita Vannucchi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Cancer Progression ◽  
Melanoma Cell ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Tissue Samples ◽  
Stress Signal ◽  
Transient Receptor ◽  
Melanoma Cell Lines

Macrophages (MΦs) and reactive oxygen species (ROS) are implicated in carcinogenesis. The oxidative stress sensor, transient receptor potential ankyrin 1 (TRPA1), activated by ROS, appears to contribute to lung and breast cancer progression. Although TRPA1 expression has been reported in melanoma cell lines, and oxidative stress has been associated with melanocytic transformation, their role in melanoma remains poorly known. Here, we localized MΦs, the final end-product of oxidative stress, 4-hydroxynonenal (4-HNE), and TRPA1 in tissue samples of human common dermal melanocytic nevi, dysplastic nevi, and thin (pT1) and thick (pT4) cutaneous melanomas. The number (amount) of intratumoral and peritumoral M2 MΦs and 4-HNE staining progressively increased with tumor severity, while TRPA1 expression was similar in all samples. Hydrogen peroxide (H2O2) evoked a TRPA1-dependent calcium response in two distinct melanoma cell lines (SK-MEL-28 and WM266-4). Furthermore, H2O2 induced a TRPA1-dependent H2O2 release that was prevented by the TRPA1 antagonist, A967079, or Trpa1 gene silencing (siRNA). ROS release from infiltrating M2 MΦs may target TRPA1-expressing melanoma cells to amplify the oxidative stress signal that affects tumor cell survival and proliferation.

scholarly journals The Human Transient Receptor Potential Melastatin 2 Ion Channel Modulates ROS Through Nrf2

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lei Bao ◽  
Fernanda Festa ◽  
Christopher S. Freet ◽  
John P. Lee ◽  
Iwona M. Hirschler-Laszkiewicz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Transient Receptor Potential ◽  
Oxidant Stress ◽  
Receptor Potential ◽  
Related Factor ◽  
Wild Type ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Nadh Generation

Abstract Transient receptor potential melastatin channel subfamily member 2 (TRPM2) has an essential role in protecting cell viability through modulation of oxidative stress. TRPM2 is highly expressed in cancer. When TRPM2 is inhibited, mitochondria are dysfunctional, ROS levels are increased, and cell viability is reduced. Here, the importance of NF-E2-related factor (Nrf2) in TRPM2-mediated suppression of oxidant stress was explored. In TRPM2 depleted cells, antioxidant cofactors glutathione, NADPH, and NADH were significantly reduced. Cytoplasmic and nuclear expression of Nrf2 and of IQGAP1, a modulator of Nrf2 stability regulated by intracellular calcium, were decreased. Antioxidant enzymes transcriptionally regulated by Nrf2 and involved in GSH, NADPH, and NADH generation were significantly lower including PRX1 and PRX3, GPX4, GSTP1, GCLC, and MTHFD2. The glutamine pathway leading to GSH production was suppressed, and ATP and GTP levels were impaired. Reconstitution with wild type TRPM2 or Nrf2, but not TRPM2 pore mutant E960D, rescued expression of enzymes downstream of Nrf2 and restored GSH and GTP. Cell viability, ROS, NADPH, NADH, and ATP levels were fully rescued by TRPM2 and partially by Nrf2. These data show that TRPM2 maintains cell survival following oxidative stress through modulation of antioxidant pathways and cofactors regulated by Nrf2.

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