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Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice.

ABSTRACT: Strongly oxidative H₂O₂ is biologically important, but if uncontrolled, would lead to tissue injuries. Lactoperoxidase (LPO) catalyzes the redox reaction of reducing highly reactive H₂O₂ to H₂O while oxidizing thiocyanate (SCN^-) to relatively tissue-innocuous hypothiocyanite (OSCN^-). SCN^- is the only known natural, effective reducing-substrate of LPO; humans normally derive SCN^- solely from food. While its enzymatic mechanism is understood, the actual biological role of the LPO-SCN^- system in mammals remains unestablished. Our group previously showed that this system protected cultured human cells from H₂O₂-caused injuries, a basis for the hypothesis that general deficiency of such an antioxidative mechanism would lead to multisystem inflammation and tumors. To test this hypothesis, we globally deleted the Lpo gene in mice. The mutant mice exhibited inflammation and lesions in the cardiovascular, respiratory, digestive or excretory systems, neuropathology, and tumors, with high incidence. Thus, this understudied LPO-SCN^- system is an essential protective mechanism in vivo.

SUBMITTER: Yamakaze J

PROVIDER: S-EPMC8203638 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice.

Yamakaze Jayden J Lu Zhe Z

Scientific reports 20210614 1

Strongly oxidative H2O2 is biologically important, but if uncontrolled, would lead to tissue injuries. Lactoperoxidase (LPO) catalyzes the redox reaction of reducing highly reactive H2O2 to H2O while oxidizing thiocyanate (SCN-) to relatively tissue-innocuous hypothiocyanite (OSCN-). SCN- is the only known natural, effective reducing-substrate of LPO; humans normally derive SCN- solely from food. W ...[more]

PMID: 34127712

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Project description:The voltage-gated potassium channels (Kv) are complex ion channels with distinct roles in neurotransmission, electrical conductivity of the heart, and smooth and striated muscle functions. Previously, we demonstrated that deletion of Kvβ2 in mice results in decreased Pax7 protein levels, hindlimb muscles and body weights, and fiber type switching. In the present study, we tested the hypothesis that Kvβ2 regulates skeletal muscle function in mice. The young and old Kvβ2 knockout (KO) and wildtype (WT) mice were utilized to test the aging phenotype and skeletal muscle function. Consistent with our previous finding, we found a significant reduction in hindlimb skeletal muscles mass and body weight in young Kvβ2 KO mice, which was also significantly reduced in old Kvβ2 KO mice compared with age-matched WT mice. Forelimb grip strength, and the hindleg extensor digitorum longus (EDL) muscles force-frequency relations were significantly decreased in young and old Kvβ2 KO mice compared to age-matched WT mice. Analysis of transmission electron microscopy images of EDL muscles in young mice revealed a significant reduction in the sarcomere length for Kvβ2 KO vs. WT. Hematoxylin and eosin-stained tibialis anterior muscles cryosections displayed a significant decrease in the number of medium (2,000-4,000 µm2) and largest (>4,000 µm2) myofibers area in young Kvβ2 KO vs. WT mice. We also found a significant increase in fibrotic tissue area in young Kvβ2 KO mice compared with age-matched WT mice. Analysis of RNA Seq data of the gastrocnemius muscles (GAS) identified significant increase in genes involved in skeletal muscle development, proliferation and cell fate determination, atrophy, energy metabolism, muscle plasticity, inflammation, and a decrease in circadian core clock genes in young Kvβ2 KO vs. WT mice. Several genes were significantly upregulated (384 genes) and downregulated (40 genes) in young Kvβ2 KO mice compared to age-matched WT mice. Further, RT-qPCR analysis of the GAS muscles displayed a significant increase in pro-inflammatory marker Il6 expression in young Kvβ2 KO mice compared to age-matched WT mice. Overall, the present study shows that deletion of Kvβ2 leads to decreased muscles strength and increased inflammation.

Dataset Information

Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice.

Publications

Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice.

Similar Datasets

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