Anna N. Bukiya, PhD

Keywords

Dietary lipids, Prenatal alcohol exposure, Alcohol and cerebral artery diameter, Cerebral artery development.

Research Objectives

The major line of interest in the lab is the lipid regulation of alcohol effect on cerebral circulation at different points during lifetime (from in utero into late adulthood). We are currently pursuing several lines. We are studying the role of dietary cholesterol in the physiology and pathology of cerebral arteries via ion channel involvement. Using rat model of high-cholesterol diet, we were the first to show that dietary cholesterol was a critical nutritional regulator of alcohol-induced constriction of cerebral arteries. Moreover, widely used statin therapy enhances alcohol-induced constriction when compared to hyperlipidemic state. After establishing the phenomenon of cholesterol control over alcohol effect at organ level, we are currently dissecting out molecular mechanisms that enable cholesterol regulation of alcohol-induced constriction of cerebral arteries at the level of large conductance, calcium- and voltage-gated potassium (BK) channel. Another line of work is focused on the fetal cerebral circulation as a target of maternal alcohol drinking. Using baboon model of pregnancy, we demonstrated that maternal binge drinking episodes reduced velocity of blood flow in fetal cerebral arteries. Remarkably, drops in blood flow velocity preceded growth restriction characteristic of alcohol-exposed fetuses. Using in vitro pressurized fetal cerebral arteries, we discovered that ethanol at physiologically relevant levels dilated fetal cerebral arteries, the dilation was blocked in presence of cannabinoid receptor antagonists. We are currently aiming at identification of novel targets of maternal drinking in fetal cerebral arteries. This work may lay a foundation for early diagnostics and successful prevention/treatment of the fetal alcohol spectrum disorders (FASD) and fetal alcohol syndrome (FAS) that are estimated to affect at least 1% of births in the USA. In addition to well-established lines of work, we have been recently focusing on the consequences of alcohol and cannabinoid consumption on cerebral arteries as well as the effects of dietary fatty acids on alcohol-induced vasoconstriction.  Laboratory maintains several active collaborations that include studies on inwardly rectifying potassium channels (Kir), and high-resolution imaging of brain vessels during fetal development.

Selected Publications

• Bukiya, A., Dopico, A., Leffler, C., Fedinec, A. (2104) Dietary cholesterol protects against alcohol-induced cerebral artery constriction. Alcohol Clin Exp Res. 38(5):1216-26.
• Bisen, S., Seleverstov, O., Belani, J., Rychnovsky, S., Dopico, A.M., Bukiya, A.N. (2016) Distinct mechanisms underlying cholesterol protection against alcohol-induced BK channel inhibition and resulting vasoconstriction. Biochim Biophys Acta. 1861(11):1756-1766.
• Bukiya, A., Seleverstov, O., Bisen, S., Dopico, A. (2016) Age-Dependent Susceptibility to Alcohol-Induced Cerebral Artery Constriction”, J Drug Alcohol Res, Volume 5, Article ID 236002.
• Bukiya, A.N., Durdagi, S., Noskov, S., Rosenhouse-Dantsker, A. (2017) Cholesterol up-regulates neuronal G protein-gated inwardly rectifying potassium (GIRK) channel activity in the hippocampus. J Biol Chem. 292(15):6135-6147.
• Bukiya, A.N., Rosenhouse-Dantsker, A. (2017) Synergistic activation of G protein-gated inwardly rectifying potassium channels by cholesterol and PI(4,5)P2. Biochim Biophys Acta. 1859(7):1233-1241.
• Seleverstov, O., Tobiasz, A., Jackson, J.S., Sullivan, R., Ma, D., Sullivan, J.P., Davison, S., Akkhawattanangkul, Y., Tate, D.L., Costello, T., Barnett, S., Li, W., Mari, G., Dopico, A.M., Bukiya, A.N. (2017) Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors. Alcohol. 61:51-61.
• Simakova, M.N., Bisen, S., Dopico, A.M., Bukiya, A.N. (2017) Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle. Biochem Pharmacol. 145:81-93.
• Tobiasz, A.M., Duncan, J.R., Bursac, Z., Sullivan, R.D., Tate, D.L., Dopico, A.M., Bukiya, A.N., Mari, G. (2018) The Effect of Prenatal Alcohol Exposure on Fetal Growth and Cardiovascular Parameters in a Baboon Model of Pregnancy. Reprod Sci. 25(7):1116-1123.
• North, K., Tobiasz, A., Sullivan, R., Bursac, Z., Duncan, J., Sullivan, J.P., Davison, S., Tate, D.L., Barnett, S., Mari, G., Bukiya, A.N. (2018) Prenatal alcohol exposure, anesthesia, and fetal loss in baboon model of pregnancy. J Drug Alcohol Res. pii: 236064, 1-11.
• Bisen, S., Simakova, M.N., Dopico, A.M., Bukiya, A.N. (2018) Large conductance voltage- and calcium-gated potassium channels (BK) in cerebral artery myocytes of perinatal fetal primates share several major characteristics with the adult phenotype. PLoS One. 13(9):e0203199.
• North, K., Bisen, S., Dopico, A.M., Bukiya, A.N. (2018) Tyrosine 450 in the Voltage- and Calcium-Gated Potassium Channel of Large Conductance Channel Pore-Forming (slo1) Subunit Mediates Cholesterol Protection against Alcohol-Induced Constriction of Cerebral Arteries. J Pharmacol Exp Ther. 367(2):234-244.
• Bisen, S., Kakhniashvili, D., Johnson, D.L., Bukiya, A.N. (2019) Proteomic Analysis of Baboon Cerebral Artery Reveals Potential Pathways of Damage by Prenatal Alcohol Exposure. Mol Cell Proteomics. 18(2):294-307.
• Bukiya, A.N., Blank, P.S., Rosenhouse-Dantsker, A. (2019) Cholesterol intake and statin use regulate neuronal G protein-gated inwardly rectifying potassium channels. J Lipid Res. 60(1):19-29.
• Simakova, M., Tobiasz, A., Sullivan, R.D., Bisen, S., Duncan, J., Sullivan, J.P., Davison, S., Tate, D.L., Barnett, S., Mari, G., Dopico, A.M., Bukiya, A.N. (2019) “Gestational age-dependent interplay between endocannabinoid receptors and alcohol in fetal cerebral arteries”. J Drug Alcohol Res, 8. pii: 236068.