FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313887275> ?p ?o ?g. }

• W4313887275 endingPage "531" @default.
• W4313887275 startingPage "521" @default.
• W4313887275 abstract "Antiretroviral drugs such as efavirenz (EFV) are essential to combat HIV infection in the brain, but little is known about how these drugs are metabolized locally. In this study, the cytochrome P450 (P450) and UDP-glucuronosyltransferase (UGT)-dependent metabolism of EFV was probed in brain microsomes from mice, cynomolgus macaques, and humans as well as primary neural cells from C57BL/6N mice. Utilizing ultra-high performance liquid chromatography high resolution mass spectrometry (uHPLC-HRMS), the formation of 8-hydroxyefavirenz (8-OHEFV) from EFV and the glucuronidation of P450-dependent metabolites 8-OHEFV and 8,14-dihydroxyefavirenz (8,14-diOHEFV) was observed in brain microsomes from all three species. The direct glucuronidation of EFV, however, was only detected in cynomolgus macaque brain microsomes. In primary neural cells treated with EFV, microglia were the only cell type to exhibit metabolism, forming 8-OHEFV only. In cells treated with the P450-dependent metabolites of EFV, glucuronidation was detected only in cortical neurons and astrocytes, revealing that certain aspects of EFV metabolism are cell-type specific. Untargeted and targeted proteomics experiments were used to identify the P450s and UGTs present in brain microsomes. Eleven P450s and 11 UGTs were detected in human brain microsomes, while 10 P450s and 15 UGTs were identified in mouse brain microsomes and 17 and 6 P450s and UGTs, respectively, were observed in macaque brain microsomes. This was the first time many of these enzymes have been noted in brain microsomes at the protein level. This study indicates the potential for brain metabolism to contribute to pharmacological and toxicological outcomes of EFV in the brain. <b>Significance Statement</b> Metabolism in the brain is understudied, and the persistence of HIV infection in the brain warrants the evaluation of how antiretroviral drugs, such as efavirenz, are metabolized in the brain. Using brain microsomes, the metabolism of efavirenz by both P450s and UGTs is established. Additionally, proteomics of brain microsomes characterizes P450s and UGTs in the brain, of which many have not yet been noted in the literature at the protein level." @default.
• W4313887275 created "2023-01-10" @default.
• W4313887275 creator A5017664983 @default.
• W4313887275 creator A5051493149 @default.
• W4313887275 creator A5057679242 @default.
• W4313887275 date "2023-01-09" @default.
• W4313887275 modified "2023-10-18" @default.
• W4313887275 title "Biotransformation of Efavirenz and Proteomic Analysis of Cytochrome P450s and UDP-Glucuronosyltransferases in Mouse, Macaque, and Human Brain-Derived In Vitro Systems" @default.
• W4313887275 cites W139881401 @default.
• W4313887275 cites W1548840271 @default.
• W4313887275 cites W1593208144 @default.
• W4313887275 cites W1600350812 @default.
• W4313887275 cites W173494530 @default.
• W4313887275 cites W1783991670 @default.
• W4313887275 cites W1876295320 @default.
• W4313887275 cites W1964376281 @default.
• W4313887275 cites W1965602271 @default.
• W4313887275 cites W1970756197 @default.
• W4313887275 cites W1974651587 @default.
• W4313887275 cites W1976538303 @default.
• W4313887275 cites W1981111259 @default.
• W4313887275 cites W1989833877 @default.
• W4313887275 cites W1995164644 @default.
• W4313887275 cites W1995254193 @default.
• W4313887275 cites W1996747410 @default.
• W4313887275 cites W1997115277 @default.
• W4313887275 cites W1999934243 @default.
• W4313887275 cites W2000839814 @default.
• W4313887275 cites W2004949728 @default.
• W4313887275 cites W2008189862 @default.
• W4313887275 cites W2008511207 @default.
• W4313887275 cites W2010724535 @default.
• W4313887275 cites W2012553198 @default.
• W4313887275 cites W2017242560 @default.
• W4313887275 cites W2023832414 @default.
• W4313887275 cites W2026270269 @default.
• W4313887275 cites W2030105860 @default.
• W4313887275 cites W2039332514 @default.
• W4313887275 cites W2040611122 @default.
• W4313887275 cites W2040984619 @default.
• W4313887275 cites W2047066766 @default.
• W4313887275 cites W2049436090 @default.
• W4313887275 cites W2055944089 @default.
• W4313887275 cites W2058816390 @default.
• W4313887275 cites W2066533692 @default.
• W4313887275 cites W2071086973 @default.
• W4313887275 cites W2073268391 @default.
• W4313887275 cites W2073331782 @default.
• W4313887275 cites W2073354537 @default.
• W4313887275 cites W2073797037 @default.
• W4313887275 cites W2079329807 @default.
• W4313887275 cites W2082018761 @default.
• W4313887275 cites W2085307854 @default.
• W4313887275 cites W2087297772 @default.
• W4313887275 cites W2094094393 @default.
• W4313887275 cites W2096811184 @default.
• W4313887275 cites W2099746597 @default.
• W4313887275 cites W2107818991 @default.
• W4313887275 cites W2109138935 @default.
• W4313887275 cites W2115118763 @default.
• W4313887275 cites W2118704857 @default.
• W4313887275 cites W2124431940 @default.
• W4313887275 cites W2125238670 @default.
• W4313887275 cites W2126347322 @default.
• W4313887275 cites W2126853583 @default.
• W4313887275 cites W2128419036 @default.
• W4313887275 cites W2139860070 @default.
• W4313887275 cites W2142677020 @default.
• W4313887275 cites W2144266807 @default.
• W4313887275 cites W2147849794 @default.
• W4313887275 cites W2150541827 @default.
• W4313887275 cites W2155858151 @default.
• W4313887275 cites W2159762941 @default.
• W4313887275 cites W2165995063 @default.
• W4313887275 cites W2167561407 @default.
• W4313887275 cites W2167728354 @default.
• W4313887275 cites W2169863124 @default.
• W4313887275 cites W2184362181 @default.
• W4313887275 cites W2313885872 @default.
• W4313887275 cites W2340305300 @default.
• W4313887275 cites W2477655956 @default.
• W4313887275 cites W2507540852 @default.
• W4313887275 cites W2545081213 @default.
• W4313887275 cites W2594556782 @default.
• W4313887275 cites W2612606194 @default.
• W4313887275 cites W2740884463 @default.
• W4313887275 cites W2747600138 @default.
• W4313887275 cites W2891587714 @default.
• W4313887275 cites W2914813565 @default.
• W4313887275 cites W2944738928 @default.
• W4313887275 cites W2960806790 @default.
• W4313887275 cites W2968713186 @default.
• W4313887275 cites W2980462462 @default.
• W4313887275 cites W2997590894 @default.
• W4313887275 cites W3018682869 @default.
• W4313887275 cites W3033438828 @default.
• W4313887275 cites W3033448136 @default.
• W4313887275 cites W3044379701 @default.

• next