PPARβ/δ Agonism Upregulates Forkhead Box A2 to Reduce Inflammation in C2C12 Myoblasts and in Skeletal Muscle

Phua, Wendy Wen Ting; Tan, Wei; Yip, Yun Sheng; Hew, Ivan Dongzheng; Wee, Jonathan Wei Kiat; Cheng, Hong Sheng; Leow, Melvin Khee–Shing; Wahli, Walter; Tan, Nguan Soon

doi:10.3390/ijms21051747

Cited by 12 publications

(10 citation statements)

References 55 publications

(61 reference statements)

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“…Another mediator of cytokine homeostasis [45], foxA2, was upregulated following benzene exposure in our study. FoxA2 expression can also be upregulated by fatty acids and peroxisome proliferator-activated receptors in skeletal muscle in the mice model [45]. Nfkbia is another detoxification gene that is also involved with inflammatory response.…”

Section: Discussionsupporting

confidence: 59%

Evaluating Phenotypic and Transcriptomic Responses Induced by Low-Level VOCs in Zebrafish: Benzene as an Example

Blount

Haimbaugh

et al. 2022

Toxics

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Urban environments are plagued by complex mixtures of anthropogenic volatile organic compounds (VOCs), such as mixtures of benzene, toluene, ethylene, and xylene (BTEX). Sources of BTEX that drive human exposure include vehicle exhaust, industrial emissions, off-gassing of building material, as well as oil spillage and leakage. Among the BTEX mixture, benzene is the most volatile compound and has been linked to numerous adverse health outcomes. However, few studies have focused on the effects of low-level benzene on exposure during early development, which is a susceptible window when hematological, immune, metabolic, and detoxification systems are immature. In this study, we used zebrafish to conduct a VOC exposure model and evaluated phenotypic and transcriptomic responses following 0.1 and 1 ppm benzene exposure during the first five days of embryogenesis (n = 740 per treatment). The benzene body burden was 2 mg/kg in 1 ppm-exposed larval zebrafish pools and under the detection limit in 0.1 ppm-exposed fish. No observable phenotypic changes were found in both larvae except for significant skeletal deformities in 0.1 ppm-exposed fish (p = 0.01) compared with unexposed fish. Based on transcriptomic responses, 1 ppm benzene dysregulated genes that were implicated with the development of hematological system, and the regulation of oxidative stress response, fatty acid metabolism, immune system, and inflammatory response, including apob, nfkbiaa, serpinf1, foxa1, cyp2k6, and cyp2n13 from the cytochrome P450 gene family. Key genes including pik3c2b, pltp, and chia.2 were differentially expressed in both 1 and 0.1 ppm exposures. However, fewer transcriptomic changes were induced by 0.1 ppm compared with 1 ppm. Future studies are needed to determine if these transcriptomic responses during embryogenesis have long-term consequences at levels equal to or lower than 1 ppm.

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Section: Discussionsupporting

confidence: 59%

Evaluating Phenotypic and Transcriptomic Responses Induced by Low-Level VOCs in Zebrafish: Benzene as an Example

Blount

Haimbaugh

et al. 2022

Toxics

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“…The results showed that the proliferation of C2C12 cells was significantly inhibited, and the cellular IL-1β and IL-18 were highly expressed. Studies have indicated that the NO antagonist L-NAME promotes the expression of C2C12 cell antigen, while SNP has the opposite effect, suggesting that NO may be involved in the downregulation of skeletal muscle inflammation (Frost et al, 2004;Boyd et al, 2006;Kumar et al, 2017;He et al, 2018;Phua et al, 2020). The apoptosis and inflammation related proteins ASC, caspase 1, and NLRP3 were detected by qRT-PCR and western blotting after L-NAME and SNP, respectively, in the C2C12 supernatant.…”

Section: Discussionmentioning

confidence: 99%

Effects of Nitric Oxide on C2C12 Cell Inflammatory Responses and Notexin-Induced Muscle Injury

et al. 2022

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Skeletal muscle injury is an acute inflammatory condition caused by an inflammatory response. To reduce inflammatory cell infiltration and relieve skeletal muscle injury, efficient treatment is urgently needed. Nitric oxide is a free radical molecule reported to have anti-inflammatory effects. In this study, we showed that NO could inhibit the inflammatory response of C2C12 cells in vitro and protect rat skeletal muscle injury from notexin in vivo. NO synthase inhibitor (L-NG-Nitroarginine Methyl Este, L-NAME) and NO donor (sodium nitroprusside dehydrate, SNP) were used to explore the vital role of lipopolysaccharides (LPSs) in LPS-stimulated C2C12 myoblasts.The expression of IL-18 and IL-1β was upregulated by L-NAME and downregulated by SNP, as indicated by the ELISA results. NO can reduce ASC, Caspase-1, and NLRP3 mRNA and protein levels. Furthermore, NO was detected in the rat model. The results of immunohistochemical staining showed that the production of DMD decreased. We conducted qRT-PCR and western blotting to detect the expression of Jo-1, Mi-2, TLR2, and TLR4 on day 6 post injury following treatment with L-NAME and SNP. The expression of Jo-1, Mi-2, TLR2, and TLR4 was upregulated by L-NAME and significantly reversed by SNP. NO can alleviate C2C12 cell inflammatory responses and protect rat skeletal muscle injury from notexin.

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“…Moreover, we predicted transcription factors at the CRY2-P7 locus and found that the FOXA2 transcription factor can specifically bind to the II genotype sequence. FOXA2 contributes to homeostasis in skeletal muscle and is essential for both estrogen and androgen transmission [33]. The PIC value of a marker is equivalent to its ability to detect polymorphisms between individuals in a population and is an indicator of the marker quality in genetic studies; the higher this ability, the greater its value [34].…”

Section: Discussionmentioning

confidence: 99%

Genetic Variations within the Bovine CRY2 Gene Are Significantly Associated with Carcass Traits

Jiang

Zhang

et al. 2022

Animals

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As an important part of the circadian rhythm, the circadian regulation factor 2 of cryptochrome (CRY2), regulates many physiological functions. Previous studies have reported that CRY2 is involved in growth and development. However, the relationship between CRY2 gene polymorphism and cattle carcass traits remains unclear. The aim of this study was to detect the possible variations of the CRY2 gene and elucidate the association between the CRY2 gene and carcass traits in the Shandong Black Cattle Genetic Resource (SDBCGR) population (n = 705). We identified a 24-bp deletion variation (CRY2-P6) and a 6-bp insertion variation (CRY2-P7) in the bovine CRY2 gene. The frequency of the homozygous II genotype is higher than the heterozygous ID genotype in both two loci. In addition, CRY2-P6 was consistent with HWE (p > 0.05). Importantly, the CRY2-P6 variant was significantly associated with 12 carcass traits, including gross weight, ribeye, high rib, thick flank, etc. and the II was the dominant genotype. The CRY2-P7 site was also significantly correlated with five traits (gross weight, beef-tongue, etc.). Collectively, these outcomes indicated that the two Indel loci in the CRY2 gene could be used for marker-assisted selection of cattle carcass traits.

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PPARβ/δ Agonism Upregulates Forkhead Box A2 to Reduce Inflammation in C2C12 Myoblasts and in Skeletal Muscle

Cited by 12 publications

References 55 publications

Evaluating Phenotypic and Transcriptomic Responses Induced by Low-Level VOCs in Zebrafish: Benzene as an Example

Evaluating Phenotypic and Transcriptomic Responses Induced by Low-Level VOCs in Zebrafish: Benzene as an Example

Effects of Nitric Oxide on C2C12 Cell Inflammatory Responses and Notexin-Induced Muscle Injury

Genetic Variations within the Bovine CRY2 Gene Are Significantly Associated with Carcass Traits

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