Danny McCaughan, Catherine Au, Alexandre Benedetto, Dejan Milatovic, Judy Aschner, Michael Aschner
We evaluated the effects of bilirubin on the nematode, C. elegans, specifically addressing the ability of bilirubin to induce oxidative stress and alter glutathione (GSH) content as measures of injury. Bilirubin exposure caused a doubling of the spectrophotometric absorption at 440 nm in wild-type C. elegans irrespective of the bilirubin concentration used, suggesting that bilirubin is readily taken up by the worms. No changes were noted in growth, phenotype or reproductive cycle at any bilirubin concentration at 24, 48, and 72 hrs. The oxidative stress inducible green fluorescent protein (GFP) expression in the gst-4::GFP strain was decreased upon exposure to bilirubin at a concentration of 0.5 mM at 24, 48 and 72 hrs. This trend was not statistically significant at 24 or 72 hrs, but did reach statistical significance at 48 hours (p < 0.05). Glutathione (GSH) content in the gst-4::GFP strain showed a significant increase as early as 20 hours post treatment with 0.5 mM bilirubin (p < 0.05). Microarray analysis showed that in bilirubin-exposed worms, 27 genes were up-regulated, and 90 genes were down-regulated (by >1.3 fold vs. controls). The transcription factor asc-1 was induced, whereas genes involved in transcription, trafficking and mitochondrial function were down-regulated. Our findings corroborate earlier findings of bilirubin's ability to act as an antioxidant, most likely by reducing the metabolic requirement in C. elegans.
{"title":"Antioxidant properties of blirubin in the model organism, <i>Caenorhabditis elegans</i>.","authors":"Danny McCaughan, Catherine Au, Alexandre Benedetto, Dejan Milatovic, Judy Aschner, Michael Aschner","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We evaluated the effects of bilirubin on the nematode, <i>C. elegans</i>, specifically addressing the ability of bilirubin to induce oxidative stress and alter glutathione (GSH) content as measures of injury. Bilirubin exposure caused a doubling of the spectrophotometric absorption at 440 nm in wild-type <i>C. elegans</i> irrespective of the bilirubin concentration used, suggesting that bilirubin is readily taken up by the worms. No changes were noted in growth, phenotype or reproductive cycle at any bilirubin concentration at 24, 48, and 72 hrs. The oxidative stress inducible green fluorescent protein (GFP) expression in the <i>gst-4::GFP</i> strain was decreased upon exposure to bilirubin at a concentration of 0.5 mM at 24, 48 and 72 hrs. This trend was not statistically significant at 24 or 72 hrs, but did reach statistical significance at 48 hours (p < 0.05). Glutathione (GSH) content in the <i>gst-4::GFP</i> strain showed a significant increase as early as 20 hours post treatment with 0.5 mM bilirubin (p < 0.05). Microarray analysis showed that in bilirubin-exposed worms, 27 genes were up-regulated, and 90 genes were down-regulated (by >1.3 fold vs. controls). The transcription factor <i>asc-1</i> was induced, whereas genes involved in transcription, trafficking and mitochondrial function were down-regulated. Our findings corroborate earlier findings of bilirubin's ability to act as an antioxidant, most likely by reducing the metabolic requirement in <i>C. elegans</i>.</p>","PeriodicalId":14115,"journal":{"name":"International journal of neuroprotection and neuroregeneration","volume":"4 3","pages":"252-262"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555407/pdf/nihms-1004066.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37038962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marta Imbesi, Tolga Uz, Sevim Yildiz, Ahmet D Arslan, Hari Manev
OBJECTIVES: In the mammalian brain, G protein-coupled MT(1) and MT(2) melatonin receptors may be involved in Alzheimer's pathology, long-term potentiation, depression, and in the behavioral effects of psychoactive drugs. These drugs; e.g. antidepressants and drugs of abuse, are typically used over long periods of time and may alter neuroplasticity and gene expression. We hypothesized that such antidepressant- and cocaine-altered expression of melatonin receptor mRNA may occur in the hippocampus and striatum. METHODOLOGY: Male C3H/HeJ mice were treated with the antidepressants fluoxetine, desipramine, and clomipramine, with the psychostimulant cocaine, and with a vehicle either a single time or once a day for 14 days. Brain samples were collected 24 h after the last injection and the content of MT(1) and MT(2) mRNA was assayed. RESULTS: A single drug injection did not alter the MT(1) and MT(2) mRNA content. In the hippocampus, protracted treatment with antidepressants increased the amount of MT(1) mRNA (with the exception of fluoxetine) but decreased MT(2) mRNA content; cocaine did not produce any alterations. In the striatum, antidepressants produced the opposite effect on MT(1) mRNA content; they decreased it. They did not significantly alter striatal MT(2) mRNA (we observed a nonsignificant trend to a decrease). Cocaine also decreased striatal MT(1) mRNA content without affecting MT(2) mRNA. CONCLUSION: These results suggest that drug- and region-specific alterations of MT(1)/MT(2) mRNA produced by protracted antidepressants and cocaine treatment may alter MT1/MT2 expression and contribute to long-term neuroplastic effects of these drugs.
{"title":"Drug- and region-specific effects of protracted antidepressant and cocaine treatment on the content of melatonin MT(1) and MT(2) receptor mRNA in the mouse brain.","authors":"Marta Imbesi, Tolga Uz, Sevim Yildiz, Ahmet D Arslan, Hari Manev","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>OBJECTIVES: In the mammalian brain, G protein-coupled MT(1) and MT(2) melatonin receptors may be involved in Alzheimer's pathology, long-term potentiation, depression, and in the behavioral effects of psychoactive drugs. These drugs; e.g. antidepressants and drugs of abuse, are typically used over long periods of time and may alter neuroplasticity and gene expression. We hypothesized that such antidepressant- and cocaine-altered expression of melatonin receptor mRNA may occur in the hippocampus and striatum. METHODOLOGY: Male C3H/HeJ mice were treated with the antidepressants fluoxetine, desipramine, and clomipramine, with the psychostimulant cocaine, and with a vehicle either a single time or once a day for 14 days. Brain samples were collected 24 h after the last injection and the content of MT(1) and MT(2) mRNA was assayed. RESULTS: A single drug injection did not alter the MT(1) and MT(2) mRNA content. In the hippocampus, protracted treatment with antidepressants increased the amount of MT(1) mRNA (with the exception of fluoxetine) but decreased MT(2) mRNA content; cocaine did not produce any alterations. In the striatum, antidepressants produced the opposite effect on MT(1) mRNA content; they decreased it. They did not significantly alter striatal MT(2) mRNA (we observed a nonsignificant trend to a decrease). Cocaine also decreased striatal MT(1) mRNA content without affecting MT(2) mRNA. CONCLUSION: These results suggest that drug- and region-specific alterations of MT(1)/MT(2) mRNA produced by protracted antidepressants and cocaine treatment may alter MT1/MT2 expression and contribute to long-term neuroplastic effects of these drugs.</p>","PeriodicalId":14115,"journal":{"name":"International journal of neuroprotection and neuroregeneration","volume":"2 ","pages":"185-9"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2286828/pdf/nihms-38187.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27365091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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