Finn, Robert

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Citation:  Finn,  Robert  (2011)  Cytochrome  P450  Monoxygenase  Complex  and  Skin  Development.  In:  Northumbria  Research  Conference,  5-6  May  2011,  Northumbria  University,  Newcastle-upon-Tyne.Published by: Northumbria  UniversityURL: This  version  was  downloaded  from  Northumbria  Research  Link:  http://nrl.northumbria.ac.uk/3361/Northumbria  University  has  developed Northumbria  Research  Link  (NRL)  to  enable users to access the University’s research output.  Copyright  © and moral  rights  for  items on NRL  are retained by the individual  author(s) and/or other  copyright  owners.  Single  copies of full  items can be reproduced, displayed or performed, and given to third  parties  in  any  format  or  medium  for  personal  research or  study,  educational,  or  not-for-profit  purposes without  prior  permission  or  charge,  provided  the  authors,  tit le  and  full  bibliographic  details  are  given,  as  well  as  a  hyperlink  and/or  URL  to  the  original  metadata  page. The content  must  not  be changed in  any way.  Full  items must  not  be sold commercially  in  any format  or medium  without  formal  permission of the copyright  holder.  The full  policy is available online: http://nrl.northumbria.ac.uk/policies.htmlThis document  may differ  from the final,  published version of the research and has been made available online in  accordance with  publisher  policies. To read and/or cite from the  published  version  of the  research,  please visit  the  publisher’s  website  (a subscription  may be required.)Abstract for Oral Presentation/Paper Cytochrome P450 Monoxygenase Complex and Skin Development. Robert D. Finn*, Olivier Sparagano*, Lesley McLaughlin^, Colin Henderson^ & C. Roland Wolf^. *School of Life Sciences, Northumbria University & ^ Cancer Research UK Molecular Pharmacology Unit, University of Dundee. Cytochromes-P450 (CYPs), the first line-defence in the detoxification of drugs/harmful chemicals, play a role in various biological processes such as fatty acid metabolism. For these functions, CYPs form a complex with P450-oxidoreductase (POR) and cytochrome-b5 (cytb5). To investigate this complex in more detail, we developed mouse models where either POR or cytb5 was knocked out in the liver or the organism as a whole. Results show the absence of POR/cytb5 has a dramatic effect on all CYP functions 1, 2. In studies involving knockout cytb5 mice, a role in skin development was identified 3. Changes observed were very similar to patients suffering from ichthyosis skin disorders 4. These disorders are associated with loss of  very long chain fatty acids. The CYP4 family function in the production of these fatty acids, therefore the defects observed in these mice maybe due to disrupted CYP4 activity. Supporting this hypothesis, genetics disruptions in CYP4F22, have been identified in patients suffering from lamellar ichthyosis 5. A role for this new CYP in very long chain fatty acid production in the skin remains unproven as does a link between its function and cytb5. This paper will report these findings and the directions which will be taken to decipher these links.  1. Finn, R.D., et.al. (2009) Unsaturated fatty acid regulation of Cytochrome P450 expression via a CAR-dependent pathway. Biochemical Journal (417): 43-54. 2. Finn, R.D., et.al. (2008) Defining the in vivo role for cytochrome b5 in Cytochrome P450 function through the conditional hepatic deletion of microsomal cytochrome b5. Journal of Biological Chemistry. 283(46): 31385-31393. 3. Finn, R.D., et.al. (2010) Cytochrome b5 null mouse: a new model for studying inherited skin disorders and the role of unsaturated fatty acids in normal homeostasis. Transgenic Research. DOI: 10.1007/s11248-010-9426-1 4. Akiyama M & Shimizu H (2008) An update on molecular aspects of the non-syndromic ichthyoses. Exp Dermatol 17(5): 373-382. 5. Lefevre, C., et al. (2006) Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. Hum Mol Genet 15(5): 767-776.  

Cytochrome P450 Monoxygenase Complex and Skin Development

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