Arsenic downregulates tight junction claudin proteins through p38 and NF-κB in intestinal epithelial cell line, HT-29

Bovine mastitis, an inflammation of the udder, results in reduced milk production and poor milk quality. Mastitis is usually, but not always, a response to pathogen infection. High milk yield can produce oxidative stress in the mammary tissue. High milk yield is also known to be associated with bovine mastitis. Thus, in the current study, we hypothesised that oxidative stress increases inflammatory responses in bovine mammary cells. To examine the hypothesis, we produced cellular oxidative stress and investigated resulting inflammatory responses in bovine mammary alveolar cells (MAC-T). To produce oxidative stress, cells were treated with the reactive oxygen species (ROS; e.g., superoxide anion)-producing agent, menadione (MD; 0-10 µm; 6 h). To ensure the ROS-induced responses, cells were pretreated with an antioxidant NAC (0-10 mm; 1 h). Results showed that MD elevated intracellular ROS levels and protein expression of cyclooxygenase-2 (COX-2), a biomarker of inflammation. Pretreatment of cells with NAC attenuated MD-induced COX-2 expression by scavenging intracellular ROS and enhancing intracellular glutathione levels. MD-induced COX-2 expression was mediated by activation of extracellular signal receptor-activated kinase 1/2 (ERK1/2), Akt, and nuclear factor-kappa B (NF-κB). NAC attenuated activation of these intracellular signalling molecules. Treatment of cells with pharmacological inhibitors for ERK1/2, Akt, and NF-κB confirmed the association of these signalling pathways in MD-induced COX-2 expression. These results support our hypothesis that oxidative stress, which is found in high-yielding dairy cows, can produce cellular inflammation in bovine mammary alveolar cells and prevention of oxidative stress can attenuate such pathological responses. This may be relevant for cases of clinical mastitis for which no pathogen can be isolated.

show abstract

“…deficiency and a general antioxidant (Jeong et al 2017). In the present study, intracellular GSH levels increased in cells treated with NAC.…”

Section: Discussionsupporting

confidence: 62%

Oxidative stress-induced inflammatory responses and effects of N-acetylcysteine in bovine mammary alveolar cells

Bae

Jeong

Cheng

et al. 2017

Journal of Dairy Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Numerous naturally occurring anti-oxidant compounds possess anti-cancer properties [12]. Oxidative stresses including hydrogen peroxide and nitric oxide decrease claudin-1 and -5 expression in colonic HT-29 cells [41], claudin-2 expression in MDCK II cells [42], and claudin-5 expression in ischemic brain [43], which are inhibited by antioxidants. Oxidative stress may be one of the key factors controlling claudins expression.…”

Section: Discussionmentioning

confidence: 99%

Kaempherol and Luteolin Decrease Claudin-2 Expression Mediated by Inhibition of STAT3 in Lung Adenocarcinoma A549 Cells

et al. 2017

View full text Add to dashboard Cite

Claudin-2 is highly expressed in human lung adenocarcinoma tissues and may be a novel target for cancer chemotherapy because knockdown of claudin-2 decreases cell proliferation. We found that flavonoids including kaempferol, chrysin, and luteolin concentration-dependently decrease claudin-2 expression in lung adenocarcinoma A549 cells. Claudin-2 expression is up-regulated by mitogen-activated protein kinase kinase (MEK)/ extracellular signal-regulated kinase (ERK)/c-Fos and phosphoinositide 3-kinase (PI3K)/Akt/nuclear factor-κB (NF-κB) pathways, but these activities were not inhibited by kaempferol, chrysin, and luteolin. Promoter deletion assay using luciferase reporter vector showed that kaempferol and luteolin inhibit the function of transcriptional factor that binds to the region between −395 and −144 of claudin-2 promoter. The decrease in promoter activity was suppressed by mutation in signal transducers and activators of transcription (STAT)-binding site, which is located between −395 and −144. The phosphorylation level of STAT3 was not decreased, but the binding of STAT3 on the promoter region is suppressed by kaempferol and luteolin in chromatin immunoprecipitation assay. The inhibition of cell proliferation caused by kaempferol and luteolin was partially recovered by ectopic claudin-2 expression. Taken together, kaempferol and luteolin decreased claudin-2 expression and proliferation in A549 cells mediated by the inhibition of binding of STAT3 on the promoter region of claudin-2. The intake of foods and nutrients rich in these flavonoids may prevent lung adenocarcinoma development.

show abstract

“…The mRNA levels of p38, extracellular signal-regulated kinase (ERK)1, ERK2, and Jun N-terminal kinase (JNK) and the protein levels of phosphorylated-JNK (p-JNK)/JNK were significantly elevated in cardiomyocytes by arsenic [137]. Arsenic damaged intestinal epithelial cells (HT-29) by increasing p38 phosphorylation [138]. It has been suggested that arsenic activates MAPK via EGFR-dependent signaling transduction, such as EGFR/MEK, EGFR/Ras/MEK, and Src/EGFR cascades [29,83,134,[139][140][141][142][143], or EGF-independent signaling pathways, such as Shc [135].…”

Section: Mapk Pathwaymentioning

confidence: 99%

The Role of Reactive Oxygen Species in Arsenic Toxicity

et al. 2020

View full text Add to dashboard Cite

Arsenic poisoning is a global health problem. Chronic exposure to arsenic has been associated with the development of a wide range of diseases and health problems in humans. Arsenic exposure induces the generation of intracellular reactive oxygen species (ROS), which mediate multiple changes to cell behavior by altering signaling pathways and epigenetic modifications, or cause direct oxidative damage to molecules. Antioxidants with the potential to reduce ROS levels have been shown to ameliorate arsenic-induced lesions. However, emerging evidence suggests that constructive activation of antioxidative pathways and decreased ROS levels contribute to chronic arsenic toxicity in some cases. This review details the pathways involved in arsenic-induced redox imbalance, as well as current studies on prophylaxis and treatment strategies using antioxidants.

show abstract

Arsenic downregulates tight junction claudin proteins through p38 and NF-κB in intestinal epithelial cell line, HT-29

Cited by 43 publications

References 53 publications

Oxidative stress-induced inflammatory responses and effects of N-acetylcysteine in bovine mammary alveolar cells

Oxidative stress-induced inflammatory responses and effects of N-acetylcysteine in bovine mammary alveolar cells

Kaempherol and Luteolin Decrease Claudin-2 Expression Mediated by Inhibition of STAT3 in Lung Adenocarcinoma A549 Cells

The Role of Reactive Oxygen Species in Arsenic Toxicity

Contact Info

Product

Resources

About