Inhibition of cathepsin B activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin

Kędzior, Mateusz; Seredyński, Rafał; Godzik, Urszula; Tomczyk, Dagmara; Gutowicz, Jan; Terlecka, Ewa; Całkosiński, Ireneusz; Terlecki, Grzegorz

doi:10.1007/s11356-014-3482-7

Cited by 5 publications

(2 citation statements)

References 40 publications

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“…increased amounts of lysosomal bodies with strong acid phosphatase activity which prevented T 4 disconnection from thyroglobulin (Collins et al, 1977). Moreover, both in vivo (Pocar et al, 2006) and in vitro experiments (Kędzior et al, 2015) revealed that dioxin and PCBs downregulate the mRNA expression and activity of cathepsin B, the enzyme responsible for solubilization of thyroglobulin and subsequent thyroid hormone liberation (Friedrichs et al, 2003). These assumptions, however, need further investigation.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the in vitro effects of TCDD, PCB 126 and PCB 153 on thyroid-restricted gene expression and thyroid hormone secretion by the chicken thyroid gland

Katarzyńska

Hrabia

Kowalik

et al. 2015

Environmental Toxicology and Pharmacology

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Section: Discussionmentioning

confidence: 99%

Comparison of the in vitro effects of TCDD, PCB 126 and PCB 153 on thyroid-restricted gene expression and thyroid hormone secretion by the chicken thyroid gland

Katarzyńska

Hrabia

Kowalik

et al. 2015

Environmental Toxicology and Pharmacology

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“…Our own studies have shown the significant effect that mechlorethamine and 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) have on hepatic metabolism [ 4 , 5 , 6 ]. In vitro studies have shown that these compounds interfere with the enzyme kinetics of cathepsin b, as well as having the ability to penetrate into lysosomes [ 7 ]. The negative effects of dioxins on hepatic metabolism were manifested by the increased frequency and severity of Disseminated Intravascular Coagulation (DIC) in induced pleurisy [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

The Improvement of the Adaptation Process of Tocopherol and Acetylsalicylic Acid in Offspring of Mothers Exposed to TCDD

Madej

Leśków

Tarnowska

et al. 2021

Animals

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Dioxins are chemical compounds that may cause an inflammatory reaction. During dioxin-induced inflammation, generated reactive oxygen species lead to morphological changes in various tissues and in biochemical parameters. The aim of this study was to demonstrate the changes in the livers of rats whose mothers were exposed to dioxins and the protective role of α-tocopherol and acetylsalicylic acid in liver inflammation. The study material consisted of Buffalo rats who were the offspring of females treated with dioxin, dioxin + α-tocopherol, or dioxin + acetylsalicylic acid. Livers and blood samples were taken from the rats’ offspring, and then histopathological and biochemical analyses were performed. The histopathological analysis showed that the changes observed in the livers of neonates were the result of the dioxins derived from their mother. The biochemical analysis showed that the morphological changes in the liver affected its function, which manifested in a higher total protein concentration in the dioxin-treated group, and that the creatinine level in this group was significantly higher than that in the other groups. This effect was reduced by the protective role of α-tocopherol and acetylsalicylic acid. Based on these results, we came to the conclusion that dioxins significantly affect the structure of the liver, which negatively affects its function, mainly in the scope of the metabolism of plasma proteins and hepatic enzymes.

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Revealing the inhibitory potential of Yersinia enterocolitica on cysteine proteases of the papain family

Kędzior

Pawlak

Seredyński

et al. 2018

Microbiological Research

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Cysteine proteases of the papain family, including mammalian cathepsins, play important physiological roles, however, their excessive activity may contribute to the development of various pathologies. Therefore, cysteine cathepsin inhibitors are being considered as promising drugs to treat cathepsin-driven diseases. Diverse saprophytic and parasitic microbes produce such inhibitors, which target the host's proteases playing pivotal roles in immune responses, thus leading to the survival of microbes within their host. Yersinia enterocolitica is a Gram-negative zoopathogenic coccobacillus, which has developed several mechanisms to evade the host's immune system. Nevertheless, the bacterium has not yet been shown to produce any cysteine protease inhibitors. Here we demonstrate that Y. enterocolitica strains of different bioserotypes and genotypes synthesize papain and human cathepsin L inhibitors, but not bovine cathepsin B inhibitors. By employing fluorimetry and zymography, the cell-surface inhibitors were shown to associate peripherally with the outer membrane, while the inhibitors present in cell-free extracts proved to: interact reversibly with their target enzymes, exhibit thermolability and stability in a range of pH values (5-9), and have high molecular weights. Batch affinity chromatography on papain-agarose resin was then undertaken to isolate putative inhibitors of cysteine proteases from the bacterial extract. The isolated 18 kDa protein was identified by LC-MS/MS as the periplasmic chaperone Skp. The Skp-containing eluate inhibited the activity of cysteine cathepsins produced by human dermal fibroblasts. The homologous Skp protein was also isolated from the extract of Escherichia coli. Our results point to a possible new biological role of the bacterial chaperone Skp.

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Inhibition of cathepsin B activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin

Cited by 5 publications

References 40 publications

Comparison of the in vitro effects of TCDD, PCB 126 and PCB 153 on thyroid-restricted gene expression and thyroid hormone secretion by the chicken thyroid gland

Comparison of the in vitro effects of TCDD, PCB 126 and PCB 153 on thyroid-restricted gene expression and thyroid hormone secretion by the chicken thyroid gland

The Improvement of the Adaptation Process of Tocopherol and Acetylsalicylic Acid in Offspring of Mothers Exposed to TCDD

Revealing the inhibitory potential of Yersinia enterocolitica on cysteine proteases of the papain family

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