Paraquat-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells: Involvement of p53 and Mitochondria

Yang, Woosung; Tiffany‐Castiglioni, Evelyn

doi:10.1080/15287390701738467

Cited by 83 publications

(56 citation statements)

References 91 publications

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“…Paraquat (N,N′-dimethyl-4,4′-bipyridinium dichloride) is a widely used herbicide that is toxic to kidney cells and functions to increase ROS levels in humans and animals through the inhibition of mitochondrial function. [32][33][34][35] Like that observed with Y 2 O 3 NPs, we found that the paraquat exposure induced a similar MTT response ( Figure 3C). The mechanism of the paraquat and the Y 2 O 3 NP cytotoxicity are similar but is not currently clear and will require further in-depth experimentation.…”

Section: Discussionsupporting

confidence: 62%

Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells

Selvaraj¹,

Bodapati²,

Murray³

et al. 2014

IJN

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Background The increased use of engineered nanoparticles (NPs) has caused new concerns about the potential exposure to biological systems and the potential risk that these materials may pose on human health. Here, we examined the effects of exposure to different concentrations (0–50 μg/mL) and incubation times (10 hours, 24 hours, or 48 hours) of yttrium oxide (Y 2 O 3 ) NPs on human embryonic kidney (HEK293) cells. Changes in cellular morphology, cell viability, cell membrane integrity, reactive oxygen species levels, mitochondrial membrane potential, cell death (apoptosis and necrosis), and the DNA damage after NP exposure were compared to the effects seen following incubation with paraquat, a known toxicant. Results The 24-hour inhibitory concentration 50 (IC 50 ) of Y 2 O 3 NPs (41±5 nm in size) in the HEK293 cells was found to be 108 μg/mL. Incubation with Y 2 O 3 NPs (12.25–50 μg/mL) increased the ratio of Bax/Bcl-2, caspase-3 expression and promoted apoptotic- and necrotic-mediated cell death in both a concentration and a time-dependent manner. Decreases in cell survivability were associated with elevations in cellular reactive oxygen species levels, increased mitochondrial membrane permeability, and evidence of DNA damage, which were consistent with the possibility that mitochondria impairment may play an important role in the cytotoxic response. Conclusion These data demonstrate that the Y 2 O 3 NP exposure is associated with increased cellular apoptosis and necrosis in cultured HEK293 cells.

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Section: Discussionsupporting

confidence: 62%

Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells

Selvaraj¹,

Bodapati²,

Murray³

et al. 2014

IJN

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“…Thus, oxidative cellular stress by PQ involves both the generation of reactive oxygen species (ROS) and mitochondrial dysfunction. The mitochondrial pathway of apoptosis has been suggested as one of the mechanisms for dopaminergic neuronal cell death by PQ (Yang and Tiffany-Castiglioni, 2008). Recently, many mechanisms of cell death other than apoptosis have been revealed .…”

Section: Introductionmentioning

confidence: 99%

Necrosis in human neuronal cells exposed to paraquat

Hirayama¹,

Aki²,

Funakoshi³

et al. 2018

J. Toxicol. Sci.

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-Paraquat (PQ) is an herbicide that was once used worldwide, but is now prohibited in many nations due to its high toxicity to humans. However, there are still rare cases of the fetal intoxication of PQ, which was purchased prior to the prohibition in Japan. In this study, several cell death pathways, the mitochondrial stress response, and autophagy were examined in SH-SY5Y cells exposed to PQ. The results reveal the decrease of a mitochondrial stress sensitive-BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) protein, the suppression of autophagic flux, and the lack of apoptosis as well as other regulated forms of necrosis, such as necroptosis and ferroptosis. Taken together, our preliminary survey of cellular responses against PQ shows that, although responses of mitochondria and autophagy are observed, subsequent cell death is necrosis. Mechanism of PQ-induced SH-SY5Y cell death should be complicated and cannot be explained thoroughly by already-known mechanisms.

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“…58 Moreover, paraquat and rotenone induce cytochrome c release 59,60 and caspase-9 activation, which are preceded by the induction/ activation of proapoptotic Bax and Bak. 61 In addition, it has been observed that 4-HT pretreatment successfully inhibited the plumbagin and juglone induced accumulation of Bax in the mitochondrial membrane, cytochrome c release, as well as caspase-3 activation in human peripheral blood lymphocytes. 63 To our knowledge this is the first report about the 4-HT mediated attenuation of various molecules involved in the cell cycle arrest and apoptotic microglial cell death induced by dichlorvos.…”

Section: -Ht Pretreatment Attenuates the Dichlorvos Mediated Change mentioning

confidence: 99%

4-Hydroxy TEMPO Attenuates Dichlorvos Induced Microglial Activation and Apoptosis

Sunkaria

Sharma

Wani

et al. 2014

ACS Chem. Neurosci.

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Microglial cells have been implicated in various neurodegenerative diseases. Previous studies from our lab have shown that dichlorvos (an organophosphate) could induce Parkinson's like features in rats. Recently, we have shown that dichlorvos can induce microglial activation, and if not checked in time could ultimately induce neuronal apoptosis. However, this activation does not always pose a threat to the neurons. Activated microglia also secrete various neuronal growth factors, suggesting that they have beneficial roles in CNS repair. Therefore, it is essential to control their detrimental functions selectively. Here, we tried to find out how microglial cells behave when exposed to dichlorvos in either the presence or absence of potent nitric oxide scavenger and superoxide dismutase mimetic, 4-hydroxy TEMPO (4-HT). Wistar rat pups (1 day) were used to isolate and culture primary microglial cells. We found 4-HT pretreatment successfully attenuated the dichlorvos mediated microglial activation. Moreover, 4-HT pretreatment decreased the up-regulated levels of p53 and its downstream effector, p21. The expression of various cell cycle regulators such as Chk2, CDC25a, and cyclin A remained close to their basal levels when 4-HT pretreatment was given. DNA fragmentation analysis showed significant reduction in the DNA damage of 4-HT pretreated microglia as compared to dichlorvos treated cells. In addition to this, we found 4-HT pretreatment prevented the microglial cells from undergoing apoptotic cell death even after 48 h of dichlorvos exposure. Taken together, our results showed 4-HT pretreatment could successfully ameliorate the dichlorvos induced microglial cell damage.

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Paraquat-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells: Involvement of p53 and Mitochondria

Cited by 83 publications

References 91 publications

Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells

Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells

Necrosis in human neuronal cells exposed to paraquat

4-Hydroxy TEMPO Attenuates Dichlorvos Induced Microglial Activation and Apoptosis

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