Ochratoxin A induces apoptosis in neuronal cells

Zhang, Xiangnan; Boesch-Saadatmandi, Christine; Lou, Yijia; Wolffram, Siegfried; Huebbe, Patricia; Rimbach, Gerald

doi:10.1007/s12263-008-0109-y

Cited by 87 publications

(68 citation statements)

References 34 publications

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“…Ochratoxin A (OTA), one of the mycotoxins with greatest public health and agroeconomic significance [1][2][3], has been reported to be toxic to stomach, intestine, liver, kidney, neurons, and immune cells [2][3][4][5][6][7][8][9][10]. Ochratoxin A further has teratogenic potency [11].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, Ochratoxin intoxication may lead to anemia [13,14] with hypochromic-microcytic erythrocytes [13]. Ochratoxin A is in part effective by triggering apoptosis [5,6,9,10,[15][16][17][18][19][20][21][22][23][24][25][26]. Mechanisms involved in the stimulation of apoptosis by ochratoxin A include oxidative stress [18,27,28] and Ca 2+ entry [29].…”

Section: Introductionmentioning

confidence: 99%

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Enhanced Apoptotic Death of Erythrocytes Induced by the Mycotoxin Ochratoxin A

Jilani

Lupescu

Zbidah

et al. 2012

Kidney Blood Press Res

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Background: The mycotoxin ochratoxin A, an agent responsible for endemic Balkan nephropathy is known to trigger apoptosis and thus being toxic to several organs including the kidney. The mechanisms involved in ochratoxin A induced apoptosis include oxidative stress. Sequelae of ochratoxin intoxication include anemia. Similar to apoptosis of nucleated cells, erythrocytes may undergo suicidal cell death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling resulting in phosphatidylserine-exposure at the cell surface. Eryptosis could be triggered by Ca²⁺-entry through oxidant sensitive unspecificcation channels increasing cytosolic Ca²⁺ activity ([Ca²⁺]_i). The Ca²⁺-sensitivity of cell membrane scrambling could be enhanced and eryptosis thus triggered by ceramide. The removal of suicidal erythrocytes may lead to anemia. Moreover, eryptotic erythrocytes could adhere to the vascular wall thus impeding microcirculation. The present study explored, whether ochratoxin A stimulates eryptosis. Methods: Fluo3-fluorescence was utilized to determine [Ca²⁺]_i, forward scatter to estimate cell volume, annexin-V-binding to identify phosphatidylserine-exposing cells, fluorescent antibodies to detect ceramide formation and hemoglobin release to quantify hemolysis. Moreover, adhesion to human vascular endothelial cells (HUVEC) was determined utilizing a flow chamber. Results: A 48 h exposure to ochratoxin A was followed by significant increase of Fluo3-fluorescencei (≥ 2.5 µM), increase of ceramide abundance (10 µM), decrease of forward scatter (≥ 5 µM) and increase of annexin-V-binding (≥ 2.5 µM). Ochratoxin A exposure slightly but significantly enhanced hemolysis (10 µM). Ochratoxin (10 µM) enhanced erythrocyte adhesion to HUVEC. Removal of extracellular Ca²⁺ significantly blunted, but did not abrogate ochratoxin A-induced annexin V binding. Conclusions: Ochratoxin A triggers suicidal erythrocyte death or eryptosis, an effect partially but not fully due to stimulation of Ca²⁺-entry.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enhanced Apoptotic Death of Erythrocytes Induced by the Mycotoxin Ochratoxin A

Jilani

Lupescu

Zbidah

et al. 2012

Kidney Blood Press Res

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“…In the case of heavy metal and pesticides, both direct neurotoxicity and indirect neurotoxicity through alteration of glial functions have been demonstrated (Aschner, 2000;Franco et al, 2010;Gaasch et al, 2007;Hazell, 2002). Previous studies have already shown that various fungal toxins or mycotoxins (mainly fumonisins, ochratoxins, and trichothecenes) are able to directly cause brain cell death (Belmadani et al, 1999;Bruinink et al, 1998;Corps et al, 2010;Islam et al, 2009;Kwon et al, 2000;Merrill et al, 1996;Osuchowski and Sharma, 2005;Pestka et al, 2008a;Purzycki and Shain, 2010;Sava et al, 2006;Zhang et al, 2009). However, only few evaluations have been conducted on the potential effect of mycotoxins on the functions of glial cells (Monnet-Tschudi et al, 1997;Razafimanjato et al, 2010;Zurich et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

The ribotoxin deoxynivalenol affects the viability and functions of glial cells

Razafimanjato

Benzaria

Taïeb

et al. 2011

Glia

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Glial cells are responsible for maintaining brain homeostasis. Modification of the viability and functions of glial cells, including astrocytes and microglia, are associated with neuronal death and neurological diseases. Many toxins (heavy metals, pesticides, bacterial or viral toxins) are known to impact on brain cell viability and functions. Although recent publications suggest a potential link between environmental exposure of humans to mycotoxins and neurological diseases, data regarding the effects of fungal toxins on brain cells are scarce. In the present study, we looked at the impact of deoxynivalenol (DON), a fungal ribotoxin, on glial cells from animal and human origin. We found that DON decreased the viability of glial cells with a higher toxicity against microglial cells compared with astrocytes. In addition to cellular toxicity, DON affected key functions of glial cells. Thus, DON caused a biphasic effect on the neuroinflammatory response of microglia to lipopolysaccharide (LPS), while sublethal doses of DON increased the LPS-induced secretion of TNF-α and nitric oxide, toxic doses inhibited it. In addition to affecting microglial functions, sublethal doses of DON also suppressed the uptake of L-glutamate by astrocytes. This inhibition was associated with a modification of the expression of the glutamate transporters at the plasma membrane. Our results suggest that environmental ribotoxins such as DON could, at low doses, cause modifications of brain homeostasis and possibly participate in the etiology of neurological diseases in which alterations of the glia are involved.

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“…Furthermore, ochratoxin exposure leads to mitochondrial impairment and bioenergetics compromise and a secondary increase in the production of ROS [296,298]. Such diminished mitochondrial performance is in part likely to be due to chronic oxidative stress, but the toxin also inhibits complex 1 of the electron transport chain and directly impairs mitochondrial membrane potential [299,300]. It is also of interest that exposure to ochratoxin A provokes atypical responses in microglia and astrocytes compromising their neuroprotective function and positively promotes neuroinflammation via the up-regulation of for example NF-κB [301,302].…”

Section: Chronic Mold and Mycotoxin Exposurementioning

confidence: 99%

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Morris¹,

Berk

Walder

et al. 2015

Mol Neurobiol

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Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

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Ochratoxin A induces apoptosis in neuronal cells

Cited by 87 publications

References 34 publications

Enhanced Apoptotic Death of Erythrocytes Induced by the Mycotoxin Ochratoxin A

Enhanced Apoptotic Death of Erythrocytes Induced by the Mycotoxin Ochratoxin A

The ribotoxin deoxynivalenol affects the viability and functions of glial cells

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

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