Neurotoxin-induced cell death in neuronal PC12 cells is mediated by induction of apoptosis

Walkinshaw, Gail; Waters, Catherine

doi:10.1016/0306-4522(94)90566-5

Cited by 189 publications

(118 citation statements)

References 28 publications

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“…As shown by phase contrast photomicroscopy (Figure 2A,B) 18 h after veratridine exposure, cells showed morphological characteristics of apoptosis, including cell shrinkage and neurite blebbing relative to vehicle treated control cultures (Sloviter et al, 1996;Walkinshaw et al, 1993). No signs of necrotic cell death (swelling and lysis) were observed.…”

Section: Am-36 and Blockade Of Veratridine Neurotoxicitymentioning

confidence: 89%

Incorporation of sodium channel blocking and free radical scavenging activities into a single drug, AM‐36, results in profound inhibition of neuronal apoptosis

Callaway¹,

Beart²,

Jarrott³

et al. 2001

British J Pharmacology

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1 AM-36 is a novel neuroprotective agent incorporating both antioxidant and Na + channel blocking actions. In cerebral ischaemia, loss of cellular ion homeostasis due to Na + channel activation, together with increased reactive oxygen species (ROS) production, are thought to contribute to neuronal death. Since neuronal death in the penumbra of the ischaemic lesion is suggested to occur by apoptosis, we investigated the ability of AM-36, antioxidants and Na + channel antagonists to inhibit toxicity induced by the neurotoxin, veratridine in cultured cerebellar granule cells (CGC's). 2 Veratridine (10 ± 300 mM) concentration-dependently reduced cell viability of cultured CGC's. Under the experimental conditions employed, cell death induced by veratridine (100 mM) possessed the characteristics of apoptosis as assessed by morphology, TUNEL staining and DNA laddering on agarose gels. 3 Neurotoxicity and apoptosis induced by veratridine (100 mM) were inhibited to a maximum of 50% by the antioxidants, U74500A (0.1 ± 10 mM) and U83836E (0.03 ± 10 mM), and to a maximum of 30% by the Na + channel blocker, dibucaine (0.1 ± 100 mM). In contrast, AM-36 (0.01 ± 10 mM) completely inhibited veratridine-induced toxicity ( IC 50 1.7 (1.5 ± 1.9) mM, 95% con®dence intervals (CI) in parentheses) and concentration-dependently inhibited apoptosis. 4 These ®ndings suggest veratridine-induced toxicity and apoptosis are partially mediated by generation of ROS. AM-36, which combines both Na + channel blocking and antioxidant activity, provided superior neuroprotection compared with agents possessing only one of these actions. This bifunctional pro®le of activity may underlie the potent neuroprotective e ects of AM-36 recently found in a stroke model in conscious rats.

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Section: Am-36 and Blockade Of Veratridine Neurotoxicitymentioning

confidence: 89%

Incorporation of sodium channel blocking and free radical scavenging activities into a single drug, AM‐36, results in profound inhibition of neuronal apoptosis

Callaway¹,

Beart²,

Jarrott³

et al. 2001

British J Pharmacology

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show abstract

“…The toxin induces morphological changes in PC-12 cells that are typical of apoptosis, including cell shrinkage, membrane blebbing, and DNA fragmentation (Walkinshaw & Waters 1994). The mitochondrial-caspase cascade is frequently activated in response to apoptotic signals.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of dimerumic acid and deferricoprogen fromMonascus purpureusNTU 568-fermented rice against 6-hydroxydopamine-induced oxidative stress and apoptosis in differentiated pheochromocytoma PC-12 cells

Tseng

Hsu

Pan

2016

Pharmaceutical Biology

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Pan (2016) Neuroprotective effects of dimerumic acid and deferricoprogen from Monascuspurpureus NTU 568-fermented rice against 6-hydroxydopamine-induced oxidative stress and apoptosis in differentiated pheochromocytoma PC-12 cells, Pharmaceutical Biology, 54:8, 1434-1444, DOI: 10.3109/13880209.2015 Objective The effects of DMA and DFC on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity and potential protective mechanisms in differentiated PC-12 pheochromocytoma cells were investigated. Materials and methods DMA (0-60 mM) or DFC (0-10 mM) was co-treated with 6-OHDA (200 mM, 24 h exposure) in differentiated PC-12 cells. Cell viability and intercellular reactive oxygen species (ROS) were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and 2 0 ,7 0 -dichlorofluorescein-diacetate (DCFH-DA) assays, respectively. Cell apoptosis was determined by DNA fragmentation analysis and propidium iodide staining by flow cytometry. Western blot analysis was used to measure the levels of cell protein expression. Results DMA and DFC significantly increased cell viability to 72% and 81% in 6-OHDA-induced differentiated PC-12 cell cultures, respectively. Furthermore, DMA and DFC reduced 6-OHDAinduced formation of extracellular and intercellular ROS by 25% and 20%, respectively, and decreased NADPH oxidase-2 expression in differentiated PC-12 cells. DMA and DFC inhibited 6-OHDA-induced apoptosis and decreased activation of caspase-3 via regulation of Bcl-2-associated X protein (Bax) and Bcl-2 protein expression in differentiated PC-12 cells. Conclusion DMA and DFC may protect against 6-OHDA toxicity by inhibiting ROS formation and apoptosis. These results showed that the metabolites from M. purpureus NTU 568 fermentation were potential therapeutic agents for PD induced by oxidative damage and should be encouraged for further research. ARTICLE HISTORY

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“…In this study, we have explored the role of the bioflavonoid antioxidant rutin on 6-OHDA-induced neurotoxicity in PC-12 cells. PC-12 cells were used as they resemble the neuronal cells at substantia nigra pars compacta in human brain (14). 6-OHDA is a neurotoxin that is usually used to induce oxidative stress in PC-12 cells.…”

Section: Discussionmentioning

confidence: 99%

Rutin, a bioflavonoid antioxidant protects rat pheochromocytoma (PC-12) cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity

Magalingam

Radhakrishnan

Haleagrahara

2013

International Journal of Molecular Medicine

101

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Neurotoxin-induced cell death in neuronal PC12 cells is mediated by induction of apoptosis

Cited by 189 publications

References 28 publications

Incorporation of sodium channel blocking and free radical scavenging activities into a single drug, AM‐36, results in profound inhibition of neuronal apoptosis

Incorporation of sodium channel blocking and free radical scavenging activities into a single drug, AM‐36, results in profound inhibition of neuronal apoptosis

Neuroprotective effects of dimerumic acid and deferricoprogen fromMonascus purpureusNTU 568-fermented rice against 6-hydroxydopamine-induced oxidative stress and apoptosis in differentiated pheochromocytoma PC-12 cells

Rutin, a bioflavonoid antioxidant protects rat pheochromocytoma (PC-12) cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity

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