title: HIV-1 Tat-mediated apoptosis in human blood-retinal barrier-associated cells.
abstract: HIV-1-associated ocular complications, such as microvasculopathies, can lead to the loss of vision in HIV-1-infected patients. Even in patients under highly active antiretroviral therapy, ocular lesions are unavoidable. Ocular complications have been demonstrated to be closely related to the breakdown of the blood-retinal-barrier (BRB); however, the underlying mechanism is not clear. The data from this study indicated that the HIV-1 Tat protein induced the apoptosis of human retinal microvascular endothelial cells (HRMECs) and retinal pigmen epithelium (RPE) cells, which compose the inner BRB and the outer BRB, respectively. In addition, this study found that the activation of N-methyl-D-aspartate receptors (NMDARs) was involved in the apoptosis of RPE cells, but it caused no changes in HRMECs. Furthermore, both cell types exhibited enhanced expression of Bak, Bax and Cytochrome c. The inhibition of Tat activity protected against the apoptosis induced by NMDAR activation and prevented the dysregulation of Bak, Bax and Cytochrome c, revealing an important role for the mitochondrial pathway in HIV-1 Tat-induced apoptosis. Together, these findings suggest a possible mechanism and may identify a potential therapeutic strategy for HIV-1-associated ocular complications.
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Che
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Fanglin
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Shiqiong
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gu
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Wang
mesh_terms: D057134:Antibodies, Neutralizing / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001813:Blood-Retinal Barrier / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009928:Organ Specificity; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D057134:Antibodies, Neutralizing; C494772:BAK1 protein, human; C494826:BAX protein, human; D016194:Receptors, N-Methyl-D-Aspartate; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D054322:tat Gene Products, Human Immunodeficiency Virus; D045304:Cytochromes c
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