Mice Deficient in the Gene for Cytochrome P450 (CYP)1A1 Are More Susceptible Than Wild-Type to Hyperoxic Lung Injury: Evidence for Protective Role of CYP1A1 Against Oxidative Stress

Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Wang, Gangduo; Couroucli, Xanthi I.; Shivanna, Binoy; Welty, Stephen E.; Barrios, Roberto; Khan, M. Firoze; Nebert, Daniel W.; Roberts, L. Jackson; Moorthy, Bhagavatula

doi:10.1093/toxsci/kfu106

Cited by 47 publications

(43 citation statements)

References 39 publications

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“…FABP4 is one of fatty acid binding proteins, and the expression of FABP4 and FABP5 was enhanced during cirrhosis in hepatocarcinogenesis of rat model (Liu et al, 2009), which was not contradictory with our result and indicated an alteration of fat metabolism. One previous study showed that cytochrome P450 (CYP) 1A1 could protect lung from oxidative injury by decreasing levels of lipid hydroperoxides (Lingappan et al, 2014), and the Present study demonstrated that CYP1A1 was upregulated at three time points and activated fatty acid metabolism at 3 and 9 weeks, suggesting that CYP1A1 may also play a protective role by activating fatty acid metabolism in liver cirrhosis. According to the IPA analysis, LPS/IL-1-mediated inhibition of RXR function ranked first in the identified canonical pathways, and the study performed by Raghu et al (2012) indicated that this pathway was involved in ethanol metabolism in alcoholic fatty liver.…”

Section: Discussionmentioning

confidence: 51%

Relationship analysis between gene expression profiles and rat liver cirrhosis occurrence

Wang¹,

Zhao²,

Chen³

et al. 2017

Afr. J. Biotechnol.

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Liver cirrhosis (LC) is a kind of liver disease which is pathologically characterized by abnormality and necrosis of hepatic cells, proliferation of fibrous tissue, nodular regeneration and pseudolobule formation. To explore the mechanism of LC occurrence at the level of mRNA, Rat Genome 230 2.0 Array was used to detect gene expression profiles of rat fibrotic livers in 3, 6 and 9 weeks after CCl 4 treatment in this study. It was found that a total of 305 genes including 153 up-regulated, 150 down-regulated and 2 up/down-regulated genes, were related to LC occurrence. Then, k-means clustering was employed to classify above 305 genes into 5 clusters based on gene expression similarity, and EASE analysis further indicated that the above genes were mainly associated with metabolic process, stress reaction, cell growth and apoptosis/death. Thereafter, ingenuity pathway analysis (IPA) software was used to analyze potential effects of the above-mentioned 305 genes, and the results suggested that lipid metabolism and cell growth were inhibited while cell apoptosis/death was activated, but immune/inflammatory response was first activated and then inhibited. Furthermore, IPA also predicted that several signal pathways "ERK/MAPK Signaling", "p38 MAPK", "Endothelin-1 Signaling", "Growth Hormone Signaling", "LPS/IL-1-mediated inhibition of RXR function" and "IL-6 Signaling" were involved in regulating the occurrence of liver cirrhosis. It was concluded that 305 genes and 3 kinds of physiological activities were closely related to LC occurrence.

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Section: Discussionmentioning

confidence: 51%

Relationship analysis between gene expression profiles and rat liver cirrhosis occurrence

Wang¹,

Zhao²,

Chen³

et al. 2017

Afr. J. Biotechnol.

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“…Cytochrome P450 enzymes induction usually enhances detoxification; thus, induction is a protective mechanism. A protective role of Cyp1a1 has been described in the lung, where elevation of Cyp1a1 decreased oxidative stress in this tissue and decreased MDA and 4-HNE, the most prominent end-products of lipid peroxidation [34]. We believe that Cyp1a1 elevation is a compensatory response by keratinocytes to combat lipid peroxidation when Ubiad1 is silenced, and may reveal the importance of Ubiad1 in keratinocyte physiology.…”

Section: Discussionmentioning

confidence: 61%

Significance of Ubiad1 for Epidermal Keratinocytes Involves More Than CoQ10 Synthesis: Implications for Skin Aging

et al. 2018

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Abstract:The significance of Coenzyme Q10 (CoQ10) as an anti-oxidant barrier of the skin, as well as a key component in anti-aging strategies for skin care products, has been firmly established. Biosynthesis of CoQ10 in the mitochondria is well known, but there is only limited information on the non-mitochondrial synthesis of CoQ10 in the skin. Recent findings in zebrafish identified that a tumor suppressor, Ubiad1, is also a key enzyme in the non-mitochondrial synthesis of CoQ10. The purpose of this study was to investigate expression of Ubiad1 in human skin, and its implication in the skin's cutaneous response to oxidative stress. We observed Ubiad1 localization in the epidermis, particularly a subcellular localization in the Golgi apparatus. Ubiad1 modulation by a pentapeptide was associated with an observed reduction in ROS/RNS stresses (−44%/−19% respectively), lipid peroxidation (−25%) and preservation of membrane fluidity under stress conditions. Electron microscopy of keratinocytes revealed a significant degree of stimulation of the Golgi complex, as well as significantly improved mitochondrial morphology. Given the importance of CoQ10 in mitigating the visible signs of skin aging, our findings identify Ubiad1 as an essential component of the defensive barriers of the epidermis.

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“…Damaged animals were likely to be experiencing oxidative stress for two reasons: increased aerobic respiration and the macrophages oxidative burst during immune response. STRING identified changes in the cytochrome P450 system, which is known to be involved in mediating oxidative stress (Lingappan et al, 2014). In addition, the full NCBI nr annotation of the differentially expressed transcripts (Supplementary Table 2) included Thioredoxin, which is involved in cellular redox homeostasis (Jones and Go, 2010).…”

Section: Month After Damagementioning

confidence: 99%

Transcriptomic response to shell damage in the Antarctic clam, Laternula elliptica: Time scales and spatial localisation

2015

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Mollusc shell is built-up by secretion from the mantle and is the result of a controlled biological process termed biomineralisation. In general mollusc shells are well characterised however, the molecular mechanisms used by molluscs to produce shell remain largely unknown. One tractable method to study molecular biomineralisation mechanisms are shell damage-repair experiments, which stimulate calcification pathways. The present study used the Antarctic clam (Laternula elliptica) as a model to better understand when and where molecular biomineralisation events occur in the mantle. Two approaches were used: one experiment used high-throughput RNA-sequencing to study molecular damage-repair responses over a 2 month time series, and a second experiment used targeted semi-quantitative PCR to investigate the spatial location of molecular mechanisms in response to damage. Shell repair in L. elliptica was slow, lasting at least 2 months, and expression results revealed different biological processes were important at varying time scales during repair. A spatial pattern in relation to a single drilled hole was revealed for some, but not all, candidate genes suggesting the mantle may be functionally zoned and can respond to damage both locally and ubiquitously across the mantle. Valuable data on the temporal and spatial response of shell damage-repair provide a baseline not only for future studies in L. elliptica, but also other molluscs.

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Mice Deficient in the Gene for Cytochrome P450 (CYP)1A1 Are More Susceptible Than Wild-Type to Hyperoxic Lung Injury: Evidence for Protective Role of CYP1A1 Against Oxidative Stress

Cited by 47 publications

References 39 publications

Relationship analysis between gene expression profiles and rat liver cirrhosis occurrence

Relationship analysis between gene expression profiles and rat liver cirrhosis occurrence

Significance of Ubiad1 for Epidermal Keratinocytes Involves More Than CoQ10 Synthesis: Implications for Skin Aging

Transcriptomic response to shell damage in the Antarctic clam, Laternula elliptica: Time scales and spatial localisation

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