Milk Components Inhibit<i>Acanthamoeba</i>-Induced Cytopathic Effect

Saravanan, Chandrassegar; Cao, Zhiyi; Kumar, Janardan; Qiu, Jiazhou; Plaut, Andrew G.; Newburg, David S.; Panjwani, Noorjahan

doi:10.1167/iovs.07-1130

Cited by 8 publications

(2 citation statements)

References 36 publications

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“…Camel samples were transported to the laboratory as soon as practical (<4 h) and were frozen at −80°C. Aqueous portion (fat-free, skimmed milk) was removed from the lipids (cream) as described before [12]. Briefly, aliquots of pooled milk samples were centrifuged at 1400 ×g for 30 minutes at 4°C, thereafter, the creamy layer consisting largely of fat was removed by filtration through a glass wool plug in a Pasteur pipette.…”

Section: Methodsmentioning

confidence: 99%

Camel Milk Modulates the Expression of Aryl Hydrocarbon Receptor-Regulated Genes,Cyp1a1, Nqo1, andGsta1, in Murine hepatoma Hepa 1c1c7 Cells

Korashy

Gendy

Alhaider

et al. 2012

Journal of Biomedicine and Biotechnology

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There is a traditional belief in the Middle East that camel milk may aid in prevention and treatment of numerous cases of cancer yet, the exact mechanism was not investigated. Therefore, we examined the ability of camel milk to modulate the expression of a well-known cancer-activating gene, Cytochrome P450 1a1 (Cyp1a1), and cancer-protective genes, NAD(P)H:quinone oxidoreductase 1 (Nqo1) and glutathione S-transferase a1 (Gsta1), in murine hepatoma Hepa 1c1c7 cell line. Our results showed that camel milk significantly inhibited the induction of Cyp1a1 gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent Cyp1a1 inducer and known carcinogenic chemical, at mRNA, protein, and activity levels in a concentration-dependent manner. In addition, camel milk significantly decreased the xenobiotic responsive element (XRE)-dependent luciferase activity, suggesting a transcriptional mechanism is involved. Furthermore, this inhibitory effect of camel milk was associated with a proportional increase in heme oxygenase 1. On the other hand, camel milk significantly induced Nqo1 and Gsta1 mRNA expression level in a concentration-dependent fashion. The RNA synthesis inhibitor, actinomycin D, completely blocked the induction of Nqo1 mRNA by camel milk suggesting the requirement of de novo RNA synthesis through a transcriptional mechanism. In conclusion, camel milk modulates the expression of Cyp1a1, Nqo1, and Gsta1 at the transcriptional and posttranscriptional levels.

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Section: Methodsmentioning

confidence: 99%

Camel Milk Modulates the Expression of Aryl Hydrocarbon Receptor-Regulated Genes,Cyp1a1, Nqo1, andGsta1, in Murine hepatoma Hepa 1c1c7 Cells

Korashy

Gendy

Alhaider

et al. 2012

Journal of Biomedicine and Biotechnology

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“…We demonstrated that IgA-depleted tears inhibit the amoeba-induced CPE, but unfractionated complete tears are three times more potent in inhibiting the amoeba-induced CPE than the IgA-depleted tears 60. Additional studies using breast milk as a model of human mucosal secretions revealed that the IgA-depleted milk also inhibited the Acanthamoeba -induced CPE 61. IgA-depleted milk proteins were fractionated into four major fractions (F1 to F4) by gel filtration on Sephadex G200.…”

Section: Acanthamoeba Mbp and Immunobiology Of Akmentioning

confidence: 90%

Pathogenesis of Acanthamoeba Keratitis

Panjwani¹

2010

The Ocular Surface

Self Cite

143

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Acanthamoeba keratitis (AK) is a serious infection of the cornea. At present, diagnosis of the disease is not straightforward and treatment is very demanding. While contact lens wear is the leading risk factor for AK, Acanthamoeba parasites are increasingly recognized as an important cause of keratitis in non-contact lens wearers. The first critical step in the pathogenesis of infection is the adhesion of the microbe to the surface of the host tissues. Acanthamoebae express a major virulence protein, the mannose-binding protein (MBP), which mediates the adhesion of amoebae to the surface of the cornea. The MBP is a transmembrane protein with characteristics of a typical cell surface receptor. Subsequent to the MBP-mediated adhesion to host cells, the amoebae produce a contact-dependent metalloproteinase and several contact-independent serine proteinases. These proteinases work in concert to produce a potent cytopathic effect (CPE) involving killing of the host cells, degradation of epithelial basement membrane and underlying stromal matrix, and penetration into the deeper layers of the cornea. In the hamster animal model, oral immunization with the recombinant MBP protects against AK, and this protection is associated with an increased level of anti-MBP IgA in tears of protected animals. Normal human tear fluid contains IgA antibodies against Acanthamoeba MBP that is likely to provide protection by inhibiting the adhesion of parasites to host cells. Indeed, in in vitro CPE assays, even a low concentration of tears (10 [MU]μL of undiluted tears per milliliter of media) almost completely inhibits Acanthamoeba-induced CPE. In addition to adherence-inhibiting, IgA-mediated protection, human tears also contain IgA-independent factors that provide protection against Acanthamoeba-induced CPE by inhibiting the activity of cytotoxic proteinases. Characterization of the CPE-inhibitory factors of human tears should lead to a better understanding of the mechanism by which the tissues of the host resist the infection and also help decode circumstances that predispose to Acanthamoeba infections.

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