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In this report, we investigated whether the enzyme glutaminase is responsible for glutamate generation by HIV\u20101 infected monocyte\u2010derived macrophages. We tested the functionality of novel small molecule inhibitors designed to specifically block the activity of glutaminase. Glutaminase inhibitors were first characterized in a kinetic assay with crude glutaminase from rat brain revealing an uncompetitive mechanism of inhibition. The inhibitors were then tested <jats:italic>in\u00a0vitro<\/jats:italic> for their ability to prevent glutamate generation by HIV\u2010infected macrophages, their effect upon macrophage viability, and HIV infection. To validate these findings, glutaminase specific siRNA was tested for its ability to prevent glutamate increase during infection. Our results show that both glutaminase specific small molecule inhibitors and glutaminase specific siRNA were effective at preventing increases in glutamate by HIV\u20101 infected macrophage. These findings support glutaminase as a potential component of the HAD pathogenic process and identify a possible therapeutic avenue for the treatment of neuroinflammatory states such as HAD.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2007.04594.x","type":"journal-article","created":{"date-parts":[[2007,5,7]],"date-time":"2007-05-07T13:41:54Z","timestamp":1178545314000},"page":"539-549","source":"Crossref","is-referenced-by-count":49,"title":["Glutamate production by HIV\u20101 infected human macrophage is blocked by the inhibition of glutaminase"],"prefix":"10.1111","volume":"102","author":[{"given":"Nathan","family":"Erdmann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianxing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia L.","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelley","family":"Herek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman","family":"Curthoys","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terry D.","family":"Hexum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Tsukamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana","family":"Ferraris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,3,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1933-04.2004"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00139-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03991.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(88)90162-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nu.15.070195.001025"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(76)90062-X"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1974.tb10752.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-2985(87)80019-0"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cnr.2006.09.009"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.4.671"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1984.tb09689.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1530168100"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.7.2769"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(99)00331-9"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(01)00315-0"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00965528"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00298-X"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4241-05.2006"},{"key":"e_1_2_7_21_1","first-page":"279","article-title":"Monosodium glutamate neurotoxicity, hyperosmolarity, and blood\u2010brain barrier dysfunction","volume":"1","author":"McCall A.","year":"1979","journal-title":"Neurobehav. 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