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Full-Text Articles in Medicine and Health Sciences
A Quantitative Lc-Ms/Ms Method For Simultaneous Determination Of Cocaine And Its Metabolites In Whole Blood, Xiabin Chen, Xirong Zheng, Kai Ding, Ziyuan Zhou, Chang-Guo Zhan, Fang Zheng
A Quantitative Lc-Ms/Ms Method For Simultaneous Determination Of Cocaine And Its Metabolites In Whole Blood, Xiabin Chen, Xirong Zheng, Kai Ding, Ziyuan Zhou, Chang-Guo Zhan, Fang Zheng
Molecular Modeling and Biopharmaceutical Center Faculty Publications
As new metabolic pathways of cocaine were recently identified, a high performance liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed to simultaneously determine cocaine and nine cocaine-related metabolites in whole blood samples. One-step solid phase extraction was used to extract all of the ten compounds and corresponding internal standards from blood samples. All compounds and internal standards extracted were separated on an Atlantis T3 (100 Å, 3 μm, 2.1 mm × 150 mm I.D) column and detected in positive ion and high sensitivity mode with multiple reaction monitoring. This method was validated for its sensitivity, linearity, specificity, accuracy, precision, …
Molecular Mechanism: The Human Dopamine Transporter Histidine 547 Regulates Basal And Hiv-1 Tat Protein-Inhibited Dopamine Transport, Pamela M. Quizon, Wei-Lun Sun, Yaxia Yuan, Narasimha M. Midde, Chang-Guo Zhan, Jun Zhu
Molecular Mechanism: The Human Dopamine Transporter Histidine 547 Regulates Basal And Hiv-1 Tat Protein-Inhibited Dopamine Transport, Pamela M. Quizon, Wei-Lun Sun, Yaxia Yuan, Narasimha M. Midde, Chang-Guo Zhan, Jun Zhu
Molecular Modeling and Biopharmaceutical Center Faculty Publications
Abnormal dopaminergic transmission has been implicated as a risk determinant of HIV-1-associated neurocognitive disorders. HIV-1 Tat protein increases synaptic dopamine (DA) levels by directly inhibiting DA transporter (DAT) activity, ultimately leading to dopaminergic neuron damage. Through integrated computational modeling prediction and experimental validation, we identified that histidine547 on human DAT (hDAT) is critical for regulation of basal DA uptake and Tat-induced inhibition of DA transport. Compared to wild type hDAT (WT hDAT), mutation of histidine547 (H547A) displayed a 196% increase in DA uptake. Other substitutions of histidine547 showed that DA uptake was not altered in H547R but decreased by 99% …
Role Of Histidine 547 Of Human Dopamine Transporter In Molecular Interaction With Hiv-1 Tat And Dopamine Uptake, Yaxia Yuan, Pamela M. Quizon, Wei-Lun Sun, Jianzhuang Yao, Jun Zhu, Chang-Guo Zhan
Role Of Histidine 547 Of Human Dopamine Transporter In Molecular Interaction With Hiv-1 Tat And Dopamine Uptake, Yaxia Yuan, Pamela M. Quizon, Wei-Lun Sun, Jianzhuang Yao, Jun Zhu, Chang-Guo Zhan
Molecular Modeling and Biopharmaceutical Center Faculty Publications
HIV-1 Tat plays an important role in HIV-associated neurocognitive disorders (HAND) by disrupting neurotransmission including dopamine uptake by human dopamine transporter (hDAT). Previous studies have demonstrated that HIV-1 Tat directly binds to hDAT and some amino-acid mutations that attenuate the hDAT-Tat binding also significantly decreased dopamine uptake activity of hDAT. This combined computational-experimental study demonstrates that histidine-547 (H547) of hDAT plays a crucial role in the hDAT-Tat binding and dopamine uptake by hDAT, and that the H547A mutation can not only considerably attenuate Tat-induced inhibition of dopamine uptake, but also significantly increase the Vmax of hDAT for dopamine uptake. …