A role for spermine oxidase as a mediator of reactive oxygen species production in HIV-Tat-induced neuronal toxicity

Capone, Caterina; Cervelli, Manuela; Angelucci, Emanuela; Colasanti, Marco; Macone, Alberto; Mariottini, Paolo; Persichini, Tiziana

doi:10.1016/j.freeradbiomed.2013.05.007

Cited by 63 publications

(58 citation statements)

References 48 publications

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“…SMOX is reported as a crucial enzyme in the polyamine catabolic pathway which plays a significant role in maintaining the polyamine homeostasis [27,51]. The involvement of SMOX in neurodegenerative diseases has been reported by other laboratories [52,53]. Elevated SMOX/APAO levels represent elevated oxidative stress resulting from elevated polyamine oxidation.…”

Section: Discussionmentioning

confidence: 92%

Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice

Liu

Saul

Pichavaram

et al. 2020

JCM

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Purpose Deregulation of polyamine metabolism has been implicated in various neurodegenerative disease and injury conditions. Studies from our laboratory have demonstrated that polyamine oxidation is a critical mediator of both neuronal and vascular injury in a mouse model of retinopathy of prematurity (Narayanan et al 2014; Patel et al 2016). The current study was undertaken to investigate the role of the polyamine oxidase spermine oxidase (SMO) in mediating neuronal damage and dysfunction in the diabetic retina. Methods Mice (8 weeks old, C57BL6J) were made diabetic by injection of streptozotocin (STZ, 65 mg/kg, pH 4.5, i.p.) and compared to age‐matched controls after 4 to 15 weeks of diabetes. Following the onset of hyperglycemia, mice were treated with either vehicle (normal saline) or SMO inhibitor, MDL 72527 (20 mg/kg of body weight, in saline, intra‐peritoneal, 3 times/week). Retinal neuronal function in living mice was determined by electroretinography (ERG). Retinal structure in the same mice was analyzed by Spectral Domain‐Optical Coherence Tomography (SD‐OCT). Following ERG and SD‐OCT analyses, mice were humanely euthanized, and retinas were collected and processed for immunofluorescence and western blot analyses. Results Western blot analysis showed that expression of SMO was increased in the diabetic retinas compared to controls. Inner retinal function studied by dark‐adapted electroretinography showed that the positive (pSTR) and negative (nSTR) scotopic threshold responses (measured at 110 ms and 200 ms), were significantly reduced (p<0.01, N=5–12) in the diabetic (4–12 weeks) mice as compared with the controls. The pSTR, but not the nSTR amplitudes were greatly improved in the MDL‐treated diabetic mice (p<0.05, N=5–10). The amplitude at 110 ms was dominated by the b‐wave at higher intensities and was significantly stronger in the MDL72527‐treated mice than in the vehicle‐treated diabetic mice. SD‐OCT analysis demonstrated a significant thinning of retina in the diabetic mice (p<0.01, N=5–12), which was improved in the MDL‐treated group. These data demonstrate a partial rescue of inner retinal function and retinal structure by SMO inhibition in the diabetic retina. Studies on the impact of MDL72527 treatment on neuronal survival are currently in progress. Conclusion Our results show the specific involvement of Spermine Oxidase in mediating neuronal injury in the diabetic retina and demonstrate its potential as a therapeutic target for mitigating neuronal injury in diabetic retinopathy. Support or Funding Information These studies supported by the National Eye Institute (1R01EY028569 to S.P.N) and Augusta University Culver Vision Discovery institute pilot grant to S.P.N. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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Section: Discussionmentioning

confidence: 92%

Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice

Liu

Saul

Pichavaram

et al. 2020

JCM

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“…In the case of H 2 O 2 , the highly sensitive, cell-permeable probe 2′,7′-dichlorofluorescin diacetate (DCFH-DA) was utilized based on Capone et al (2013). Images were captured with an inverted fluorescence microscope system (Axio Observer A1, Zeiss, Germany) using standard filters and collection modalities for DHE yellow fluorescence (excitation 515 nm; emission 525 nm) and for DCFH-DA green fluorescence (excitation 488 nm; emission 525 nm).…”

Section: Methodsmentioning

confidence: 99%

Sub-high Temperature and High Light Intensity Induced Irreversible Inhibition on Photosynthesis System of Tomato Plant (Solanum lycopersicum L.)

et al. 2017

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High temperature and high light intensity is a common environment posing a great risk to organisms. This study aimed to elucidate the effects of sub-high temperature and high light intensity stress (HH, 35°C, 1000 μmol⋅m-2⋅s-1) and recovery on the photosynthetic mechanism, photoinhibiton of photosystem II (PSII) and photosystem I (PSI), and reactive oxygen (ROS) metabolism of tomato seedlings. The results showed that with prolonged stress time, net photosynthetic rate (Pn), Rubisco activity, maximal photochemistry efficiency (Fv/Fm), efficient quantum yield and electron transport of PSII [Y(II) and ETR(II)] and PSI [Y(I) and ETR(I)] decreased significantly whereas yield of non-regulated and regulated energy dissipation of PSII [Y(NO) and Y(NPQ)] increased sharply. The donor side limitation of PSI [Y(ND)] increased but the acceptor side limitation of PSI [Y(NA)] decreased. Content of malondialdehyde (MDA) and hydrogen peroxide (H2O2) were increased while activity of superoxide dismutase (SOD) and peroxidase (POD) were significantly inhibited compared with control. HH exposure affected photosynthetic carbon assimilation, multiple sites in PSII and PSI, ROS accumulation and elimination of Solanum lycopersicum L.

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“…The first involves the NADPH (but not xanthine) oxidases [86]. The second implies the induction of spermine oxidase (SMO), an enzyme involved in the catabolism of biogenic polyamines [88, 97]. The third relies on mitochondrial dysfunction [98] but was questioned in a later study [86].…”

Section: Mechanisms Of Ros Production During Hiv Infectionmentioning

confidence: 99%

Oxidative Stress during HIV Infection: Mechanisms and Consequences

Ivanov

Valuev-Elliston

Иванова

et al. 2016

Oxidative Medicine and Cellular Longevity

285

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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A role for spermine oxidase as a mediator of reactive oxygen species production in HIV-Tat-induced neuronal toxicity

Cited by 63 publications

References 48 publications

Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice

Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice

Sub-high Temperature and High Light Intensity Induced Irreversible Inhibition on Photosynthesis System of Tomato Plant (Solanum lycopersicum L.)

Oxidative Stress during HIV Infection: Mechanisms and Consequences

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