Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunodeficiency observed in HIV-1-infected patients is mainly due to uninfected bystander CD4+ T lymphocyte cell death. The viral envelope glycoproteins (Env), expressed at the surface of infected cells, play a key role in this process. Env triggers macroautophagy/autophagy, a process necessary for subsequent apoptosis, and the production of reactive oxygen species (ROS) in bystander CD4+ T cells. Here, we demonstrate that Env-induced oxidative stress is responsible for their death by apoptosis. Moreover, we report that peroxisomes, organelles involved in the control of oxidative stress, are targeted by Env-mediated autophagy. Indeed, we observe a selective autophagy-dependent decrease in the expression of peroxisomal proteins, CAT and PEX14, upon Env exposure; the downregulation of either BECN1 or SQSTM1/p62 restores their expression levels. Fluorescence studies allowed us to conclude that Env-mediated autophagy degrades these entire organelles and specifically the mature ones. Together, our results on Env-induced pexophagy provide new clues on HIV-1-induced immunodeficiency. Abbreviations: Ab: antibodies; AF: auranofin; AP: anti-proteases; ART: antiretroviral therapy; BafA1: bafilomycin A1; BECN1: beclin 1; CAT: catalase; CD4: CD4 molecule; CXCR4: C-X-C motif chemokine receptor 4; DHR123: dihydrorhodamine 123; Env: HIV-1 envelope glycoproteins; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; GFP-SKL: GFP-serine-lysine-leucine; HEK: human embryonic kidney; HIV-1: type 1 human immunodeficiency virus; HTRF: homogeneous time resolved fluorescence; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NAC: N-acetyl-cysteine; PARP: poly(ADP-ribose) polymerase; PEX: peroxin; ROS: reactive oxygen species; siRNA: small interfering ribonucleic acid; SQSTM1/p62: sequestosome 1.
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PMID:HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4+ T cell death. 3307 73

Nephrotoxicity is a dose-limiting side effect of long-term use of tenofovir, a reverse transcriptase inhibitor that is used for the treatment of HIV infection and chronic hepatitis B infection. Identifying an agent that prevents tenofovir disoproxil fumarate (TDF)-induced renal injury can lead to its better tolerance, and a more effective treatment can be achieved. The present study is aimed at investigating whether melatonin, a potent antioxidant and anti-inflammatory agent, protects against TDF nephrotoxicity in rats and to determine its cellular targets. Rats were divided into groups and treated as follows. Group I (control): Rats in this group (n = 6) received sterile water only by gavage for 35 days. Group II: Rats (n = 6) in this group received 600 mg/kg body weight TDF in sterile water by gavage for 35 days. Group III: Rats (n = 6) in this group received once daily 20 mg/kg bodyweight melatonin i.p. 2 h before the administration of 600 mg/kg body weight TDF in sterile water by gavage for 35 days. Group IV: Rats were pretreated daily with 20 mg/kg body weight melatonin i.p. 2 h before the administration of sterile water by gavage. All the rats were sacrificed on the 36th day, after overnight fast. Melatonin pretreatment protected the rats against TDF nephrotoxicity both histologically and biochemically. Biochemically, melatonin pretreatment attenuated TDF-induced, oxidative stress, nitrosative stress, mitochondrial pathway of apoptosis, PARP overactivation and preserved proximal tubular function (p < 0.01). This suggests that melatonin may be useful in ameliorating TDF nephrotoxicity.
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PMID:Melatonin protects against tenofovir-induced nephrotoxicity in rats by targeting multiple cellular pathways. 3314 23


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