<i>Clostridium botulinum</i> neurotoxin A induces apoptosis and mitochondrial oxidative stress via activation of TRPM2 channel signaling pathway in neuroblastoma and glioblastoma tumor cells

Akpınar, Orhan; Özşimşek, Ahmet; Güzel, Mustafa; Nazıroğlu, Mustafa

doi:10.1080/10799893.2020.1781174

Cited by 22 publications

(36 citation statements)

References 36 publications

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“…However, the data in cancer models mostly supports the conclusion that TRPM2 expression and function have an important role in preserving cancer cell viability and survival. Consistent with this view, the TRPM2 channel has been found to be highly expressed in numerous cancers including bladder, breast, head and neck, lung, pancreatic, prostate, melanoma, and neuroblastoma [ 51 ], among which most studies were focused on the neuroblastoma [ 58 , 59 , 60 , 61 , 62 , 63 , 64 ] ( Figure 2 ). The higher levels of ROS in cancer cells impel the enhancement of their anti-oxidant capacity to detoxify ROS and preserve cells viability.…”

Section: Transient Receptor Potential Melastatin 2 (Trpm2) Channelmentioning

confidence: 62%

Roles of NAD+ and Its Metabolites Regulated Calcium Channels in Cancer

Cai

Liang

et al. 2020

Molecules

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Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor for redox enzymes, but also moonlights as a regulator for ion channels, the same as its metabolites. Ca2+ homeostasis is dysregulated in cancer cells and affects processes such as tumorigenesis, angiogenesis, autophagy, progression, and metastasis. Herein, we summarize the regulation of the most common calcium channels (TRPM2, TPCs, RyRs, and TRPML1) by NAD+ and its metabolites, with a particular focus on their roles in cancers. Although the mechanisms of NAD+ metabolites in these pathological processes are yet to be clearly elucidated, these ion channels are emerging as potential candidates of alternative targets for anticancer therapy.

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Section: Transient Receptor Potential Melastatin 2 (Trpm2) Channelmentioning

confidence: 62%

Roles of NAD+ and Its Metabolites Regulated Calcium Channels in Cancer

Cai

Liang

et al. 2020

Molecules

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“…Intracellular ROS levels in HK-2 cells were evaluated by dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining as previously described ( 45 , 46 ). HK-2 cells were initially cultured in 6-well plates for 48 h and DCFH- DA fluorescent dye (10 µM) was added and incubated for 20 min at 37°C in the dark and then were washed with PBS.…”

Section: Methodsmentioning

confidence: 99%

Salusin‑β participates in high glucose‑induced HK‑2 cell ferroptosis in a Nrf‑2‑dependent manner

et al. 2021

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Ferroptosis is critically involved in the pathophysiology of diabetic nephropathy (DN). As a bioactive peptide, salusin-β is abundantly expressed in the kidneys. However, it is unclear whether salusin-β participates in the pathologies of diabetic kidney damage by regulating ferroptosis. The present study found that high glucose (HG) treatment upregulated the protein expressions of salusin-β in a dose-and time-dependent manner. Genetic knockdown of salusin-β retarded, whereas overexpression of salusin-β aggravated, HG-triggered iron overload, antioxidant capability reduction, massive reactive oxygen species production and lipid peroxidation in HK-2 cells. Mechanistically, salusin-β inactivated nuclear factor erythroid-derived 2-like 2 (Nrf-2) signaling, thus contributing to HG-induced ferroptosis-related changes in HK-2 cells. Notably, the protein expression of salusin-β was upregulated by ferroptosis activators, such as erastin, RSL3, FIN56 and buthionine sulfoximine. Pretreatment with ferrostatin-1 (a ferroptosis inhibitor) prevented the upregulated protein expression of salusin-β in HK-2 cells exposed to HG. Taken together, these results suggested that a positive feedback loop between salusin-β and ferroptosis primes renal tubular cells for injury in diabetes.

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“…For the determination of apoptosis levels, we used a Biocolor APOPercentage apoptosis kit (Cat #A1000, County Antrim, Northern Ireland) [37,38]. For the apoptosis analyses, the cells were added to 24-black well plates, and the analyses were performed in an Infinite 200 PRO automatic plate reader (Tecan Ltd., Männedorf, Switzerland) after adding the required reagents.…”

Section: The Determination Of Apoptosis Cell Viability Cas3 and Cas9mentioning

confidence: 99%

Hydroxychloroquine Attenuates Acute Inflammation (LPS)-Induced Apoptosis via Inhibiting TRPV1 Channel/ROS Signaling Pathways in Human Monocytes

Güzel

Akpınar

2021

Biology

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Acute inflammation (INF) and apoptosis are induced in monocytes by the generation of several factors, including the products of cytosolic oxygen free radicals (cROS) and the excessive influx of Ca2+ via the stimulation of TRPV1. These are main factors in the etiology of monocyte activation-induced inflammatory and neurodegenerative diseases. Importantly, the protective action of hydroxychloroquine (HCQ) treatment via the inhibition of TRPV1 on the levels of inflammatory factors, cROS, and apoptosis in acute INF (lipopolysaccharide, LPS)-exposed neuronal cells was recently reported. However, the relationships between acute INF via TRPV1 activation and HCQ in monocytes have not been fully clarified yet. The cell membrane of U937 human monocytes contains natural TRPV1. In the study plan, we used U937 cells in four main groups, namely control, HCQ (60 μM for 48 h), INF (1 μg/mL LPS for 16 h), and HCQ + INF. The current data indicate that LPS-induced acute INF caused the upregulation of excessive cytosolic Ca2+ accumulation via the stimulation of TRPV1 in the cells. The treatment of INF additionally upregulated the levels of apoptosis and cytokines (IL6, IL1β, and TNFα), due to upregulated cROS and lipid peroxidation levels as well as upregulated generation of caspase -3 (CAS3) and -9 (CAS9) but a decrease in glutathione and glutathione peroxidase. The expression levels of TRPV1, Bax, CAS3, and CAS9 were also upregulated by the treatment of LPS. However, treatment with HCQ and TRPV1 blocker (capsazepine) modulated the levels of cytokines, caspases, cROS, Ca2+ influx, and apoptosis through the modulation of TRPV1 in the U937 that were stimulated with LPS. In summary, the present data suggest TRPV1 activation through the acute INF (LPS)-induced inflammatory, oxidant, and apoptotic adverse actions in monocyte cells, whereas HCQ prevented adverse actions via the modulation of TRPV1. The results may be significant in the modulation of monocyte activation-caused inflammatory and neurodegenerative diseases.

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Clostridium botulinum neurotoxin A induces apoptosis and mitochondrial oxidative stress via activation of TRPM2 channel signaling pathway in neuroblastoma and glioblastoma tumor cells

Cited by 22 publications

References 36 publications

Roles of NAD+ and Its Metabolites Regulated Calcium Channels in Cancer

Roles of NAD+ and Its Metabolites Regulated Calcium Channels in Cancer

Salusin‑β participates in high glucose‑induced HK‑2 cell ferroptosis in a Nrf‑2‑dependent manner

Hydroxychloroquine Attenuates Acute Inflammation (LPS)-Induced Apoptosis via Inhibiting TRPV1 Channel/ROS Signaling Pathways in Human Monocytes

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