Signal transduction mechanism in response to aflatoxin B1 exposure: protein kinase C activity

Mistry, K.J.; Krishna, M. Bala; Pasupathy, K.; Murthy, Vadiraja V.; Bhattacharya, R.K.

doi:10.1016/0009-2797(96)03698-8

Cited by 12 publications

(8 citation statements)

References 26 publications

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“…To further test the hypothesis that aflatoxins can activate PKC activity, we utilized a Förster resonance energy transfer (FRET)-based PKC construct, CKAR 48 49 . Because AFs activate PKC in a variety of cell types 29 30 31 50 , we hypothesized that the mechanism of activation was not cell-type dependent. As primary sinonasal ALIs are very difficult to transfect, even with viral systems, CKAR was transfected into A549 cells, a commonly used lung epithelial cell line.…”

Section: Resultsmentioning

confidence: 99%

“…There is some evidence that airway cells can activate aflatoxins in vitro 4 25 and in vivo 26 27 28 , though the link between aflatoxin exposure and human lung cancer is unclear. However, aflatoxins can increase protein kinase C (PKC) activity in some cell lines in vitro 29 30 31 . Because PKC can decrease CBF 32 33 through phosphorylation of ciliary proteins 32 33 , we hypothesized that aflatoxins may have acute effects on MCC that contribute to A. flavus pathogenesis.…”

mentioning

confidence: 99%

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Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function

Lee

Workman

Carey

et al. 2016

Sci Rep

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Aflatoxins are mycotoxins secreted by Aspergillus flavus, which can colonize the respiratory tract and cause fungal rhinosinusitis or bronchopulmonary aspergillosis. A. flavus is the second leading cause of invasive aspergillosis worldwide. Because many respiratory pathogens secrete toxins to impair mucociliary immunity, we examined the effects of acute exposure to aflatoxins on airway cell physiology. Using air-liquid interface cultures of primary human sinonasal and bronchial cells, we imaged ciliary beat frequency (CBF), intracellular calcium, and nitric oxide (NO). Exposure to aflatoxins (0.1 to 10 μM; 5 to 10 minutes) reduced baseline (~6–12%) and agonist-stimulated CBF. Conditioned media (CM) from A. fumigatus, A. niger, and A. flavus cultures also reduced CBF by ~10% after 60 min exposure, but effects were blocked by an anti-aflatoxin antibody only with A. flavus CM. CBF reduction required protein kinase C but was not associated with changes in calcium or NO. However, AFB2 reduced NO production by ~50% during stimulation of the ciliary-localized T2R38 receptor. Using a fluorescent reporter construct expressed in A549 cells, we directly observed activation of PKC activity by AFB2. Aflatoxins secreted by respiratory A. flavus may impair motile and chemosensory functions of airway cilia, contributing to pathogenesis of fungal airway diseases.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function

Lee

Workman

Carey

et al. 2016

Sci Rep

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“…Previous studies demonstrated that protein biosynthesis is weakened due to the formation of AFB 1 -DNA adducts. In addition, AFB 1 could change the activity of enzymes such as cyclic nucleotide phosphodiesterase, protein kinase, and Ca 2+ -ATPase, alter hepatic protein phosphorylation ( Mistry et al, 1996 ; Ricordy et al, 2002 ), and causes p53 mutation which may develop carcinogenesis in experimental animals ( Aguilar et al, 1994 ). Similarly, our data showed that Nrf2 mRNA and protein expression level significantly down-regulated in AFB 1 -fed group.…”

Section: Discussionmentioning

confidence: 99%

Dual Role of Dietary Curcumin Through Attenuating AFB1-Induced Oxidative Stress and Liver Injury via Modulating Liver Phase-I and Phase-II Enzymes Involved in AFB1 Bioactivation and Detoxification

et al. 2018

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It is well understood that liver cytochrome p450 enzymes are responsible for AFB1 bioactivation, while phase-II enzymes regulated by the transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2) are involved in detoxification of AFB1. In this study, we explored the potential of curcumin to prevent AFB1-induced liver injury by modulating liver phase-I and phase-II enzymes along with Nrf2 involved in AFB1 bioactivation and detoxification. Arbor Acres broiler were divided into four groups including control group (G1; fed only basal feed), curcumin alone-treated group (G2; 450 mg/kg feed), AFB1-fed group (G3; 5 mg/kg feed), and curcumin plus AFB1 group (G4; 5 mg AFB1+450 mg curcumin/kg feed). After 28 days, liver and blood samples were collected for different analyses. Histological and phenotypic results revealed that AFB1-induced liver injury was partially ameliorated by curcumin supplementation. Compared to AFB1 alone-treated group, serum biochemical parameters and liver antioxidant status showed that curcumin supplementation significantly prevented AFB1-induced liver injury. RT-PCR and western blot results revealed that curcumin inhibited CYP enzymes-mediated bioactivation of AFB1 at mRNA and protein level. Transcription factor Nrf2, its downstream genes such as GSTA3, and GSTM2 mRNA, and protein expression level significantly upregulated via dietary curcumin. In addition, GSTs enzyme activity was enhanced with dietary curcumin which plays a crucial role in AFB1-detoxification. Conclusively, the study provided a scientific basis for the use of curcumin in broiler’s diet and contributed to explore the multi-target preventive actions of curcumin against AFB1-induced liver injury through the modulation of phase-I and phase-II enzymes, and its potent anti-oxidative effects.

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“…FB1 induces protein kinase C translocation via direct interaction with diacylglycerol site that also binds phorbol esters. Because phorbol esters are well-known tumor promoters, it is a more plausible cellular mechanism to explain the carcinogenicity of FB1 [46,47]. Other studies suggested that the concept that FB1-induced mitogenesis might be the mechanism of carcinogenesis and that the primary target organs are the kidney and liver [48].…”

Section: The Mechanism Of Mycotoxic Carcinogenesismentioning

confidence: 99%

The Neurological Significance of Abnormal Natural Killer Cell Activity in Chronic Toxigenic Mold Exposures

Anyanwu¹,

Jones²,

Ehiri³

et al. 2003

The Scientific World JOURNAL

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Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40° C (104°F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range of neurological consequences, some of which were headache, general debilitating pains, fever, cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, and seizures.

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Signal transduction mechanism in response to aflatoxin B1 exposure: protein kinase C activity

Cited by 12 publications

References 26 publications

Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function

Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function

Dual Role of Dietary Curcumin Through Attenuating AFB1-Induced Oxidative Stress and Liver Injury via Modulating Liver Phase-I and Phase-II Enzymes Involved in AFB1 Bioactivation and Detoxification

The Neurological Significance of Abnormal Natural Killer Cell Activity in Chronic Toxigenic Mold Exposures

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