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• W3189457299 endingPage "737266" @default.
• W3189457299 startingPage "737266" @default.
• W3189457299 abstract "Infectious bacterial and viral diseases that cause hemolysis are considered life-threatening to grass carp (Ctenopharyngodon idellus), which is a species used in aquaculture worldwide. After heme and hemeproteins (Hbs) are released as a result of hemolysis, pro-inflammatory responses and cell apoptosis occur. Heme oxygenase (HO)-1, a rate-limiting enzyme in heme catabolism, results in the formation of equivalent amounts of biliverdin (BV), carbon monoxide (CO), and ferrous iron (Fe2+). In mammals, many researchers have reported that HO-1 and its metabolites have anti-inflammatory, anti-proliferation, anti-oxidative, and anti-apoptotic effects in the process of maintaining cellular homeostasis. However, the mechanisms underlying the anti-oxidative and anti-apoptotic effects against Hb and heme of teleost HO-1 are poorly understood. To decipher the mechanisms, transcriptomic profiles of the pEGFP-HO-1 or pEGFP-N1 overexpressing in CIK cells after Hb incubation were compared. We show that the mRNA expression levels of pro-inflammatory cytokines, including TNF-α, IL-6, IL-8, IL-1β, and CCL1 were all remarkably down-regulated in the HO-1 overexpressing CIK cells after Hb and heme incubation, while HO-1 over-expression caused a significant increase in the transcriptional level expression of two anti-inflammatory cytokines, IL-10 and TGF-β, by NF-κB inhibition. Further, HO-1 over-expression dramatically induced Nrf2-Keap1 antioxidant signaling pathway-related genes, namely CAT, GSH, SOD, Keap1a, Keap1b, GST, GPX, and GR to eliminate excessive ROS production in CIK cells. Moreover, overexpression of HO-1 significantly inhibited the mRNA expression levels of the following apoptosis-related genes: FasL, Fas, FADD, TNFR1, Apaf1, p53, Bad1, Bad2, Bax, Bid, CytoC, caspase3, caspase8, and caspase9. Conversely, overexpression of HO-1 dramatically activated the mRNA expression levels of anti-apoptosis-related genes, namely Bcl-xl, Bcl2, and Mcl1. These results reveal that overexpression of HO-1 plays a significant role in cell survival by inhibiting Fas, the TNF-α death receptor pathway, and the mitochondrial pathway. In summary, HO-1 overexpression decreases inflammatory cytokine secretion and down-regulated the expression of pro-apoptotic genes and the generation of ROS may both depend on NF-κB, Fas, TNF-α death receptor and mitochondrial pathway inhibition, Nrf2-Keap1 as well as p38 MAPKs activation." @default.
• W3189457299 created "2021-08-16" @default.
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• W3189457299 date "2022-01-01" @default.
• W3189457299 modified "2023-10-16" @default.
• W3189457299 title "Heme oxygenase-1 protects against inflammatory and apoptosis induced by hemeproteins in Ctenopharyngodon Idellus kidney cells" @default.
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• W3189457299 doi "https://doi.org/10.1016/j.aquaculture.2021.737266" @default.
• W3189457299 hasPublicationYear "2022" @default.
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