Chronic Exposure to Environmentally Relevant Concentrations of Microcystin-Leucine Arginine Causes Lung Barrier Damage through PP2A Activity Inhibition and Claudin1 Ubiquitination

Abstract

Microcystin-leucine arginine (MC-LR), ubiquitous in water and food, is a threat to public health. In the present study, after C57BL/6J mice were fed with environmental concentrations of MC-LR (0, 1, 30, 60, 90, and 120 μg/L) for 6, 9, and 12 months, it was found that MC-LR could enter into mouse lung tissues and cause microstructural damage, as shown by western blotting and HE staining. Electron microscopy examination showed that MC-LR could damage the lung barrier by disruption of the tight junctions, which was confirmed by the decreased expression of tight junction markers, including Occludin, Claudin1, and ZO-1. In addition, MC-LR also increased the ubiquitination of Claudin1, indicating that MC-LR could disrupt tight junctions by promoting the degradation of Claudin1. Furthermore, MC-LR increased the levels of TNF-α and IL-6 in mouse lung tissues, leading to pneumonia. Importantly, pretreatment with PP2A activator D-erythro-sphingosine (DES) was found to significantly alleviate MC-LR-induced decrease of Occludin and Claudin1 by inhibiting the P-AKT/Snail pathway in vitro. Together, this study revealed that chronic exposure to MC-LR causes lung barrier damage, which involves PP2A activity inhibition and enhancement of Claudin1 ubiquitination. This study broadens the awareness of the toxic effects of MC-LR on the respiratory system, which has deep implications for public health.

Combination Effect of Microcystins and Arsenic Exposures on CKD: A Case-Control Study in China

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Hawthorn fruit extract protect against MC‐LR‐induced hepatotoxicity by attenuating oxidative stress and apoptosis

“…It has been found more than 279 microcystin variants, and microcystin‐LR (MC‐LR) is one of the most widely distributed and most toxic congeners 17,18 . MC‐LR has adverse effects on liver, kidney, gonad and other organs after entering the body 19,20 . Importantly, MC‐LR has strong hepatotoxicity 21 .…”

“…17,18 MC-LR has adverse effects on liver, kidney, gonad and other organs after entering the body. 19,20 Importantly, MC-LR has strong hepatotoxicity. 21 Humans or animals exposed to MC-LR could cause a range of liver damage.…”

Ultrasensitive Aptasensor for Microcystin-LR Detection in Food Samples Based on Target-Activated Assembly of Y-Shaped Hairpin Probes

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