Real-time monitoring of superoxide generation and cytotoxicity in neuroblastoma mitochondria induced by 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline

Boulton, Sarah Jayne; Keane, P.C.; Morris, Christopher M.; McNeil, Calum J.; Manning, Philip

doi:10.1179/1351000212y.0000000011

Cited by 9 publications

(6 citation statements)

References 36 publications

(39 reference statements)

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“…On the one hand, B-CA can undergo an N-methylation reaction on the second position, and the derived compound is an analogue of the 1-methyl-4-phenylpyridinium ion (MPP+), which can have mitochondrial cytotoxic effects, since its accumulation can lead to oxidative stress, which blocks the complex I of the mitochondrial electrons transport chain [89]. Diversely, some researchers suggested that B-CA has anti-oxidant properties against reactive oxygen species (ROS), possibly reducing cell damage [78].…”

Section: β-Carbolines Alkaloidsmentioning

confidence: 99%

Toxicological Aspects and Determination of the Main Components of Ayahuasca: A Critical Review

et al. 2019

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Ayahuasca is a psychoactive beverage prepared traditionally from a mixture of the leaves and stems of Psychotria viridis and Banisteriopsis caapi, respectively, being originally consumed by indigenous Amazonian tribes for ritual and medicinal purposes. Over the years, its use has spread to other populations as a means to personal growth and spiritual connection. Also, the recreational use of its isolated compounds has become prominent. The main compounds of this tea-like preparation are N,N-dimethyltryptamine (DMT), β-Carbolines, and harmala alkaloids, such as harmine, tetrahydroharmine, and harmaline. The latter are monoamine-oxidase inhibitors and are responsible for DMT psychoactive and hallucinogenic effects on the central nervous system. Although consumers defend its use, its metabolic effects and those on the central nervous system are not fully understood yet. The majority of studies regarding the effects of this beverage and of its individual compounds are based on in vivo experiments, clinical trials, and even surveys. This paper will not only address the toxicological aspects of the ayahuasca compounds but also perform a comprehensive and critical review on the analytical methods available for their determination in biological and non-biological specimens, with special focus on instrumental developments and sample preparation approaches.

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Section: β-Carbolines Alkaloidsmentioning

confidence: 99%

Toxicological Aspects and Determination of the Main Components of Ayahuasca: A Critical Review

et al. 2019

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“…They were able to establish the transmembrane flux of superoxide anions into the extracellular space through voltage-dependent anion channels (VDACs), in other words, key neurotransmission elements. Boulton et al [22] evaluated the neurotoxicity of 1trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) in SH-SY5Y neuroblastoma cells by assaying superoxide production from isolated mitochondria with an amperometric biosensor. It should be noted, however, that, contrary to our approach, this method required the fractionation of cellular organelles and as such could not be used for continuous monitoring of superoxide anion production from intact cells.…”

Section: Journal Of Sensorsmentioning

confidence: 99%

Noninvasive Superoxide Monitoring ofIn VitroNeuronal Differentiation Using a Cell-Based Biosensor

Moschopoulou¹,

Kintzios

2015

Journal of Sensors

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Membrane-engineered cells bearing superoxide dismutase (SOD) molecules on their surface offer the capability of ultrarapid and ultrasensitive detection of the superoxide anion (O2-) through the measurement of changes of their cell membrane potential. We herewith report the application of this technology for the noninvasive determination of superoxide levels during thein vitrodifferentiation of PC12 cells. We were able to detect changes inO2-accumulation in the culture medium, which were closely associated with the progress of neuronal differentiation.

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“…However, it should be noted that the role of complex II appears to be greater than previously assumed even in liver as portrayed by the 3NP results. The addition of this other commonly used complex II inhibitor shows a degree of inhibition which is comparable to that observed using the other complex I inhibitor TaClo [28]. Interestingly, although 3NP is a well-documented RC inhibitor, the emphasis in the literature in terms of numbers of studies remains biased towards the complex I and III inhibitors, rotenone and antimycin, with an additional focus on (rat) liver and muscle studies as opposed to skin.…”

Section: Resultsmentioning

confidence: 60%

A role for human mitochondrial complex II in the production of reactive oxygen species in human skin

et al. 2014

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The mitochondrial respiratory chain is a major generator of cellular oxidative stress, thought to be an underlying cause of the carcinogenic and ageing process in many tissues including skin. Previous studies of the relative contributions of the respiratory chain (RC) complexes I, II and III towards production of reactive oxygen species (ROS) have focussed on rat tissues and certainly not on human skin which is surprising as this tissue is regularly exposed to UVA in sunlight, a potent generator of cellular oxidative stress. In a novel approach we have used an array of established specific metabolic inhibitors and DHR123 fluorescence to study the relative roles of the mitochondrial RC complexes in cellular ROS production in 2 types of human skin cells. These include additional enhancement of ROS production by exposure to physiological levels of UVA. The effects within epidermal and dermal derived skin cells are compared to other tissue cell types as well as those harbouring a compromised mitochondrial status (Rho-zero A549). The results show that the complex II inhibitor, TTFA, was the only RC inhibitor to significantly increase UVA-induced ROS production in both skin cell types (P<0.05) suggesting that the role of human skin complex II in terms of influencing ROS production is more important than previously thought particularly in comparison to liver cells. Interestingly, two-fold greater maximal activity of complex II enzyme was observed in both skin cell types compared to liver (P<0.001). The activities of RC enzymes appear to decrease with increasing age and telomere length is correlated with ageing. Our study showed that the level of maximal complex II activity was higher in the MRC5/hTERT (human lung fibroblasts transfected with telomerase) cells than the corresponding wild type cells (P=0.0012) which can be considered (in terms of telomerase activity) as models of younger and older cells respectively.

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Real-time monitoring of superoxide generation and cytotoxicity in neuroblastoma mitochondria induced by 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline

Cited by 9 publications

References 36 publications

Toxicological Aspects and Determination of the Main Components of Ayahuasca: A Critical Review

Toxicological Aspects and Determination of the Main Components of Ayahuasca: A Critical Review

Noninvasive Superoxide Monitoring ofIn VitroNeuronal Differentiation Using a Cell-Based Biosensor

A role for human mitochondrial complex II in the production of reactive oxygen species in human skin

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