A Novel Role of Proline Oxidase in HIV-1 Envelope Glycoprotein-induced Neuronal Autophagy

Pandhare, Jui; Dash, Sabyasachi; Jones, Bobby; Villalta, Fernando; Dash, Chandravanu

doi:10.1074/jbc.m115.652776

Cited by 30 publications

(34 citation statements)

References 82 publications

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“…The enhancement of ROS production is mediated by the envelope protein Gp120 [79–85], Tat [83, 84, 86–88], Nef [89–91], Vpr [71, 92, 93], and reverse transcriptase (RT) [94]. …”

Section: Mechanisms Of Ros Production During Hiv Infectionmentioning

confidence: 99%

“…Interestingly, however, EPR analysis of the HIV-1 infected monocyte-derived macrophages revealed no increase in the production of either hydroxyl or other oxygen radicals [96]. In neuroblastoma cells, Gp120 was shown to induce proline oxidase (POX) that produces pyrroline-5-carboxylate with a concomitant generation of ROS (Figure 1) [85]. …”

Section: Mechanisms Of Ros Production During Hiv Infectionmentioning

confidence: 99%

“…The induction of SMO may therefore represent an important mechanism of the HIV-induced brain damage. Finally, recent data of Pandhare et al revealed that Gp120-mediated induction of proline oxidase leads to autophagy that at least partially alleviates neurotoxicity [85]. …”

Section: Ros In Hiv-1 Related Pathologiesmentioning

confidence: 99%

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Oxidative Stress during HIV Infection: Mechanisms and Consequences

Ivanov

Valuev-Elliston

Иванова

et al. 2016

Oxidative Medicine and Cellular Longevity

292

246

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It is generally acknowledged that reactive oxygen species (ROS) play crucial roles in a variety of natural processes in cells. If increased to levels which cannot be neutralized by the defense mechanisms, they damage biological molecules, alter their functions, and also act as signaling molecules thus generating a spectrum of pathologies. In this review, we summarize current data on oxidative stress markers associated with human immunodeficiency virus type-1 (HIV-1) infection, analyze mechanisms by which this virus triggers massive ROS production, and describe the status of various defense mechanisms of the infected host cell. In addition, we have scrutinized scarce data on the effect of ROS on HIV-1 replication. Finally, we present current state of knowledge on the redox alterations as crucial factors of HIV-1 pathogenicity, such as neurotoxicity and dementia, exhaustion of CD4+/CD8+ T-cells, predisposition to lung infections, and certain side effects of the antiretroviral therapy, and compare them to the pathologies associated with the nitrosative stress.

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“…The enhancement of ROS production is mediated by the envelope protein Gp120 [79–85], Tat [83, 84, 86–88], Nef [89–91], Vpr [71, 92, 93], and reverse transcriptase (RT) [94]. …”

Section: Mechanisms Of Ros Production During Hiv Infectionmentioning

confidence: 99%

Section: Mechanisms Of Ros Production During Hiv Infectionmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative Stress during HIV Infection: Mechanisms and Consequences

Ivanov

Valuev-Elliston

Иванова

et al. 2016

Oxidative Medicine and Cellular Longevity

292

246

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“…Thus, we also tested two different concentrations (50 and 200 ng/mL) of gp120 at the present study. In addition, These two gp120 concentrations used here have been indicated to have physiological relevance in some other studies (Louboutin and Strayer, 2012; Pandhare et al, 2015). SH-SY5Y is a human neuroblastoma cell line expressing N-methyl-D-aspartic acid (NMDA) receptors, CXCR4, CCR5, and but not CD4, and can binds to gp120 proteins.…”

Section: Resultsmentioning

confidence: 57%

ASPP2 Plays a Dual Role in gp120-Induced Autophagy and Apoptosis of Neuroblastoma Cells

et al. 2017

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HIV invasion of the central nervous system (CNS) in the majority of patients infected with HIV-1, leads to dysfunction and injury within the CNS, showing a variety of neurological symptoms which was broadly termed HIV-associated neurocognitive disorder (HAND). But the molecular mechanisms are not completely understood. It has been suggested that apoptosis and autophagic dysfunction in neurons may play an important role in the development of HAND. Previous studies have indicated that p53 may be involved in the onset of neurological disorder in AIDS. Apoptosis-stimulating protein of p53-2 (ASPP2), a p53-binding protein with specific function of inducing p53, has been reported to modulate autophagy. In the present study, we observed that gp120 induces autophagy and apoptosis in SH-SY5Y neuroblastoma cells. Adenovirus-mediated overexpression of ASPP2 significantly inhibited autophagy and apoptosis induced by low dose of gp120 protein (50 ng/mL), but induced autophagy and apoptosis when treated by high dose of gp120 protein (200 ng/mL). Further, ASPP2 knockdown attenuated autophagy and apoptosis induced by gp120.Conclusion: ASPP2 had different effects on the autophagy and apoptosis of neurons induced by different concentration of gp120 protein. It may be a potential therapeutic agent for HAND through modulating autophagy and apoptosis in CNS.

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“…In cancers, proline has been reported to act as a responder to nutrient and oxygen deprivation in autophagy [16]. Moreover, in the last few years, proline has been investigated for its distinctive metabolic functions in neuronal autophagy [17]. Although many reports have confirmed proline’s unique autophagic functions, the utilization of this amino acid as a regulator of autophagy in the intestine remains unexplored.…”

Section: Introductionmentioning

confidence: 99%

Na+/H+ Exchanger Regulates Amino Acid-Mediated Autophagy in Intestinal Epithelial Cells

Shi

Zhao

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Dysfunctional autophagy has been reported to be associated with aberrant intestinal metabolism. Amino acids can regulate autophagic activity in intestinal epithelial cells (IECs). Na⁺/H⁺-exchanger 3 (NHE3) has been found to participate in the absorption of amino acids in the intestine, but whether NHE3 is involved in the regulation of autophagy in IECs is unclear. Methods: In the present study, an amino acid starvation-induced autophagic model was established. Then, the effects of alanine and proline with or without the NHE inhibitor 5-(N-ethyl-N-isopropyl) amiloride (EIPA) were evaluated. Autophagy was examined based on the microtubule-associated light chain 3 (LC3) levels, transmission electron microscopy (TEM), tandem GFP-mCherry-LC3 construct, sequestosome-1 (SQSTM1, P62) mRNA and protein levels, and autophagy-related gene (ATG) 5, 7, and 12 expression levels. The autophagic flux was evaluated as the ratio of yellow (autophagosomes) to red (autolysosomes) LC3 puncta. Results: Following amino acid starvation, we found the LC3-II and ATG expression levels were enhanced in the IEC-18 cells. An increase in the number of autophagic vacuoles was concomitantly observed by TEM and confocal microscopy. Based on the results, supplementation with either alanine or proline depressed autophagy in the IEC-18 cells. Consistent with the elevated LC3-II levels, ATG expression increased upon NHE3 inhibition. Moreover, the mCherry-GFP-LC3 autophagic puncta representing both autophagosomes and autolysosomes per cell increased after EIPA treatment. Conclusions: These results demonstrate that NHE (most likely NHE3) may participate in the amino acid regulation of autophagy in IECs, which would aid in the design of better treatments for intestinal inflammation.

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A Novel Role of Proline Oxidase in HIV-1 Envelope Glycoprotein-induced Neuronal Autophagy

Cited by 30 publications

References 82 publications

Oxidative Stress during HIV Infection: Mechanisms and Consequences

Oxidative Stress during HIV Infection: Mechanisms and Consequences

ASPP2 Plays a Dual Role in gp120-Induced Autophagy and Apoptosis of Neuroblastoma Cells

Na+/H+ Exchanger Regulates Amino Acid-Mediated Autophagy in Intestinal Epithelial Cells

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