Irina A Pikuleva

Summary

Affiliation: Case Western Reserve University
Country: USA

Publications

  1. Pikuleva I, Waterman M. Cytochromes p450: roles in diseases. J Biol Chem. 2013;288:17091-8 pubmed publisher
    ..In this minireview, we describe medically significant human P450s (from families 2, 4, 7, 11, 17, 19, 21, 24, 27, 46, and 51) and the diseases associated with these P450s. ..
  2. Mast N, Lin J, Pikuleva I. Marketed Drugs Can Inhibit Cytochrome P450 27A1, a Potential New Target for Breast Cancer Adjuvant Therapy. Mol Pharmacol. 2015;88:428-36 pubmed publisher
    ..More medications on the US market may have unanticipated off-target inhibition of CYP27A1, and we propose strategies for their identification. ..
  3. van Lier J, Mast N, Pikuleva I. Cholesterol hydroperoxides as substrates for cholesterol-metabolizing cytochrome P450 enzymes and alternative sources of 25-hydroxycholesterol and other oxysterols. Angew Chem Int Ed Engl. 2015;54:11138-42 pubmed publisher
    ..CYP27A1 may participate in the removal of harmful autoxidation products in these tissues, while providing a complementary source of 25-hydroxycholesterol, a modulator of immune cell function and mediator of viral cell entry. ..
  4. Lin J, Mast N, Bederman I, Li Y, Brunengraber H, Björkhem I, et al. Cholesterol in mouse retina originates primarily from in situ de novo biosynthesis. J Lipid Res. 2016;57:258-64 pubmed publisher
  5. Anderson K, Mast N, Hudgens J, Lin J, Turko I, Pikuleva I. Mapping of the Allosteric Site in Cholesterol Hydroxylase CYP46A1 for Efavirenz, a Drug That Stimulates Enzyme Activity. J Biol Chem. 2016;291:11876-86 pubmed publisher
    ..On the basis of the data obtained, we propose the mechanism of CYP46A1 allostery and the pathway for the signal transmission from the P450 allosteric site to the active site. ..
  6. Saadane A, Mast N, Charvet C, Omarova S, Zheng W, Huang S, et al. Retinal and nonocular abnormalities in Cyp27a1(-/-)Cyp46a1(-/-) mice with dysfunctional metabolism of cholesterol. Am J Pathol. 2014;184:2403-19 pubmed publisher
    ..Our findings demonstrate the importance of retinal cholesterol metabolism for maintenance of the normal retina, and suggest new targets for diseases affecting the retinal vasculature. ..
  7. Mast N, Saadane A, Valencia Olvera A, Constans J, Maxfield E, Arakawa H, et al. Cholesterol-metabolizing enzyme cytochrome P450 46A1 as a pharmacologic target for Alzheimer's disease. Neuropharmacology. 2017;123:465-476 pubmed publisher
    ..We suggest that CYP46A1 activation by efavirenz could be a new anti-Alzheimer's disease treatment and a tool to study and identify normal and pathological brain processes affected by cholesterol maintenance. ..
  8. Lam M, Mast N, Pikuleva I. Drugs and Scaffold That Inhibit Cytochrome P450 27A1 In Vitro and In Vivo. Mol Pharmacol. 2018;93:101-108 pubmed publisher
    ..We confirmed our previous finding that CYP27A1 is a druggable enzyme and found additional drugs as well as the scaffold with potential for partial CYP27A1 inhibition in humans. ..
  9. Mast N, Zheng W, Stout C, Pikuleva I. Antifungal Azoles: Structural Insights into Undesired Tight Binding to Cholesterol-Metabolizing CYP46A1. Mol Pharmacol. 2013;84:86-94 pubmed publisher
    ..Therefore, structural understanding of the azole binding not only to CYPs 51 from the pathogenic species but also to different human P450s is required to deal efficiently with this challenge. ..

More Information

Publications12

  1. Saadane A, Mast N, Dao T, Ahmad B, Pikuleva I. Retinal Hypercholesterolemia Triggers Cholesterol Accumulation and Esterification in Photoreceptor Cells. J Biol Chem. 2016;291:20427-39 pubmed publisher
  2. Mast N, Anderson K, Lin J, Li Y, Turko I, Tatsuoka C, et al. Cytochrome P450 27A1 Deficiency and Regional Differences in Brain Sterol Metabolism Cause Preferential Cholestanol Accumulation in the Cerebellum. J Biol Chem. 2017;292:4913-4924 pubmed publisher
    ..We identified a new physiological role of CYP46A1, an important brain enzyme and cytochrome P450 that could be activated pharmacologically. ..
  3. Mast N, Anderson K, Johnson K, Phan T, Guengerich F, Pikuleva I. In vitro cytochrome P450 46A1 (CYP46A1) activation by neuroactive compounds. J Biol Chem. 2017;292:12934-12946 pubmed publisher
    ..Collectively, our in vitro data, along with those from previous cell culture and in vivo studies by others, suggest that l-Glu-induced CYP46A1 activation is of physiological relevance. ..