Selenium enhances TRPA1 channel-mediated activity of temozolomide in SH-SY5Y neuroblastoma cells

Özkal, Birol

doi:10.1007/s00381-020-04567-w

Cited by 6 publications

(7 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, we demonstrated the expression of TRPA1 channels at both the gene and protein levels in SH-SY5Y cells. Previously, TRPA1 activity has been reported in these cells [ 36 ], but TRPA1 expression was not evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…Apparently, TRPA1 serves as an integrator of inflammatory signaling secondary to the activation of GPCRs [ 47 , 48 ]. PTX treatment involves the induction of oxidative stress, specifically the accumulation of H 2 O 2 [ 36 ], thereby releasing and the CGRP sensory neuropeptide [ 19 ]. Furthermore, inhibition of TRPA1 channels reduced cold and mechanical allodynia induced by PTX [ 19 ], which suggests a strong interaction of PTX and kinase signaling, thus involving TRPA1 activity in the mechanisms of inflammatory pain [ 41 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…The macroscopic current values were normalized as pA/pF. Single TRPA1 channel activity was investigated using inside-out patch clamp recordings [36]. Single channel unitary current (i) was determined from the best fit Gaussian distribution of amplitude histograms.…”

Section: Electrophysiological Recordingsmentioning

confidence: 99%

See 2 more Smart Citations

Paclitaxel Regulates TRPA1 Function and Expression Through PKA and PKC

et al. 2022

View full text Add to dashboard Cite

Paclitaxel (PTX) is a frequently used anticancer drug that causes peripheral neuropathy. Transient receptor potential ankyrin 1 (TRPA1), a plasma membrane calcium channel, has been associated with PTX toxicity and with other chemotherapy agents such as oxaliplatin and vincristine. However, the effect of PTX on the functional expression and calcium currents of TRPA1 has not been determined. The present study shows the effect of PTX on TRPA1 activity in a neuronal cell line (SH-SY5Y). The effect of PTX on the expression of TRPA1 was assessed through quantitative PCR and Western blot analyses to determine the relative mRNA and protein expression levels. To assess the effect on calcium flux and currents, cells were exposed to PTX; simultaneously, a specific agonist and antagonist of TRPA1 were added to evaluate the differential response in exposed versus control cells. To assess the effect of PKA, PKC and PI3K on PTX-induced TRPA1 increased activity, selective inhibitors were added to these previous experiments. PTX increased the mRNA and protein expression of TRPA1 as well as the TRPA1-mediated Ca2+ currents and intracellular Ca2+ concentrations. This effect was dependent on AITC (a selective specific agonist) and was abolished with HC-030031 (a selective specific antagonist). The inhibition of PKA and PKC reduced the effect of PTX on the functional expression of TRPA1, whereas the inhibition of PI3K had no effects. PTX-induced neuropathy involves TRPA1 activity through an increase in functional expression and is regulated by PKA and PKC signaling. These findings support the role of the TRPA1 channel in the mechanisms altered by PTX, which can be involved in the process that lead to chemotherapy-induced neuropathy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Paclitaxel Regulates TRPA1 Function and Expression Through PKA and PKC

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Then, by using the commercial kit CellEvent™ Caspase-3/7 Green Detection Reagent [ 36 , 37 ], we demonstrated that AITC and H 2 O 2 evoked an early increase in caspase-3/7 activation, which was suppressed by inhibiting TRPA1-mediated Ca 2+ entry. Likewise, TRPA1 was found to mediate oxidative stress-dependent caspase-3 activation and apoptosis in temozolomide-treated SH-SY5Y neuroblastoma cells [ 51 ] and in mouse retina undergoing ischemia-reperfusion injury [ 52 ]. Therefore, TRPA1 activation in mCRC cells supports ROS-dependent apoptosis rather than cell survival, as otherwise reported in breast and lung cancers [ 8 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

Transient receptor potential ankyrin 1 (TRPA1) mediates reactive oxygen species-induced Ca2+ entry, mitochondrial dysfunction, and caspase-3/7 activation in primary cultures of metastatic colorectal carcinoma cells

et al. 2023

View full text Add to dashboard Cite

Colorectal carcinoma (CRC) represents the fourth most common cancer worldwide and is the third most common cause of malignancy-associated mortality. Distant metastases to the liver and lungs are the main drivers of CRC-dependent death. Pro-oxidant therapies, which halt disease progression by exacerbating oxidative stress, represent an antitumour strategy that is currently exploited by chemotherapy and ionizing radiation. A more selective strategy to therapeutically exploit reactive oxygen species (ROS) signaling would consist in targeting a redox sensor that is up-regulated in metastatic cells and is tightly coupled to the stimulation of cancer cell death programs. The non-selective cation channel, Transient Receptor Potential Ankyrin 1 (TRPA1), serves as a sensor of the cellular redox state, being activated to promote extracellular Ca2+ entry by an increase in oxidative stress. Recent work demonstrated that TRPA1 channel protein is up-regulated in several cancer types and that TRPA1-mediated Ca2+ signals can either engage an antiapoptotic pro-survival signaling pathway or to promote mitochondrial Ca2+ dysfunction and apoptosis. Herein, we sought to assess for the first time the outcome of TRPA1 activation by ROS on primary cultures of metastatic colorectal carcinoma (mCRC cells). We found that TRPA1 channel protein is up-regulated and mediates enhanced hydrogen peroxide (H2O2)-induced Ca2+ entry in mCRC cells as compared to non-neoplastic control cells. The lipid peroxidation product 4-hydroxynonenal (4-HNE) is the main ROS responsible for TRPA1 activation upon mCRC cell exposure to oxidative stress. TRPA1-mediated Ca2+ entry in response to H2O2 and 4-HNE results in mitochondrial Ca2+ overload, followed by mitochondrial depolarization and caspase-3/7 activation. Therefore, targeting TRPA1 could represent an alternative strategy to eradicate metastatic CRC by enhancing its sensitivity to oxidative stress.

show abstract

“…The increase in intracellular Ca 2+ and ROS levels induces the molecular cascade leading to apoptosis. Finally, the nucleic acid, protein, and lipid substances in the cell structure are transformed due to increased oxidative stress and mitochondrial depolarization [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

Activated TRPA1 plays a therapeutic role in TMZ resistance in glioblastoma by altering mitochondrial dynamics

Chen

et al. 2022

BMC Mol and Cell Biol

View full text Add to dashboard Cite

Background Glioblastoma (GBM) represents nearly one-half of primary brain tumors, and the median survival of patients with GBM is only 14.6 months. Surgery followed by radiation with concomitant temozolomide (TMZ) therapy is currently the standard of care. However, an increasing body of evidence suggests that GBM acquires resistance to TMZ, compromising the effect of the drug. Thus, further exploration into the mechanism underlying this resistance is urgently needed. Studies have demonstrated that TMZ resistance is associated with DNA damage, followed by altered reactive oxygen species (ROS) production in mitochondria. Studies have also showed that Ca2+-related transient receptor potential (TRP) channels participate in GBM cell proliferation and metastasis, but the detailed mechanism of their involvement remain to be studied. The present study demonstrates the role played by TRPA1 in TMZ resistance in GBM and elucidates the mechanism of resistance. Methods U251 and SHG-44 cells were analyzed in vitro. A CCK-8 assay was performed to verify the effect of TMZ toxicity on GBM cells. Intracellular ROS levels were detected by DCFH-DA assay. A MitoSOX Red assay was performed to determine the mitochondrial ROS levels. Intracellular Ca2+ levels in the cells were determined with a Fluo-4 AM calcium assay kit. Intracellular GSH levels were determined with GSH and GSSG Assay Kit. MGMT protein, Mitochondrial fission- and fusion-, apoptosis- and motility-related protein expression was detected by western blot assay. A recombinant lentiviral vector was used to infect human U251 cells to overexpress shRNA and generate TRPA1+/+ and negative control cells. All experiments were repeated. Results In the U251 and SHG-44 cells, TMZ induced a small increase in the apoptosis rate and intracellular and mitochondrial ROS levels. The expression of antioxidant genes and antioxidants in these cells was also increased by TMZ. However, pretreatment with a TRPA1 agonist significantly decreased the level of antioxidant gene and antioxidants expression and enhanced intracellular and mitochondrial ROS levels. Also TMZ induced the level of MGMT protein increased, and pretreatment with a TRPA1 agonist decreased the MGMT expression. Moreover, Ca2+ influx, mitochondrial damage and cell apoptosis were promoted, and the balance between mitochondrial fission and fusion protein expression was disrupted in these GBM cells. Pretreatment with a TRPA1 inhibitor slightly enhanced the level of antioxidant gene expression and reduced the apoptosis rate. TRPA1 gene overexpression in the U251 cells was similar to that after inhibitor intervention, confirming the aforementioned experimental results. Conclusion The present study proved that activating TRPA1 in glioma cells, which leads to mitochondrial damage and dysfunction and ultimately to apoptosis, may decrease the TMZ resistance of GBM cells.

show abstract

Selenium enhances TRPA1 channel-mediated activity of temozolomide in SH-SY5Y neuroblastoma cells

Cited by 6 publications

References 47 publications

Paclitaxel Regulates TRPA1 Function and Expression Through PKA and PKC

Paclitaxel Regulates TRPA1 Function and Expression Through PKA and PKC

Transient receptor potential ankyrin 1 (TRPA1) mediates reactive oxygen species-induced Ca2+ entry, mitochondrial dysfunction, and caspase-3/7 activation in primary cultures of metastatic colorectal carcinoma cells

Activated TRPA1 plays a therapeutic role in TMZ resistance in glioblastoma by altering mitochondrial dynamics

Contact Info

Product

Resources

About