Differentiating the Effects of Oxidative Stress Tests on Biopharmaceuticals

Heinzl, Geoffrey; Lai, Lo; Rao, V. Ashutosh

doi:10.1007/s11095-019-2627-2

Cited by 6 publications

(3 citation statements)

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“…Redox-active metals such as copper and iron have well established mechanisms of metal-catalyzed protein oxidation 22 , 26 . MCO induces both protein carbonylation and DOPA formation in recombinant proteins 16 . Therefore, we hypothesized that redox-active free metal ions in plasma play a critical role for elevating plasma protein carbonylation in COVID-19 plasma samples, as demonstrated by our study.…”

Section: Discussionmentioning

confidence: 99%

“…DOPA formation was detected using a fluorescence-based detection method as previously described 16 . Plasma samples (40 µg each) were diluted with 300 µL of 100 mM sodium phosphate pH 9.2 and treated with 300 µL of 20 mM 4-(aminomethyl)-benzenesulfonic acid (ABS) prepared in 100 mM sodium phosphate pH 9.2.…”

Section: Methodsmentioning

confidence: 99%

“…residues in proteins are susceptible to oxidation under oxidative stress conditions that may impact protein quality. Tyrosine oxidation to 3,4 dihydroxyphenylalanine (DOPA) has been previously reported to be a common modification under oxidative stress conditions16,18 . We used a fluorescence-based method to measure DOPA levels in the plasma samples.…”

mentioning

confidence: 99%

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Metal-induced oxidative stress and human plasma protein oxidation after SARS-CoV-2 infection

Aryal

Tillotson

et al. 2023

Sci Rep

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Pathogenesis of COVID-19 by SARS-CoV-2 resulted in a global pandemic and public health emergency in 2020. Viral infection can induce oxidative stress through reactive oxygen species (ROS). Inflammation and environmental stress are major sources of oxidative stress after infection. Micronutrients such as iron, copper, zinc, and manganese play various roles in human tissues and their imbalance in blood can impact immune responses against pathogens including SARS CoV-2. We hypothesized that alteration of free metal ions during infection and metal-catalyzed oxidation plays a critical role towards pathogenesis after infection. We analyzed convalescent and hospitalized COVID-19 patient plasma using orthogonal analytical techniques to determine redox active metal concentrations, overall protein oxidation, oxidative modifications, and protein levels via proteomics to understand the consequences of metal-induced oxidative stress in COVID-19 plasma proteins. Metal analysis using ICP-MS showed significantly greater concentrations of copper in COVID-19 plasma compared to healthy controls. We demonstrate significantly greater total protein carbonylation, other oxidative modifications, and deamidation of plasma proteins in COVID-19 plasma compared to healthy controls. Proteomics analysis showed that levels of redox active proteins including hemoglobulin were elevated in COVID-19 plasma. Molecular modeling concurred with potential interactions between iron binding proteins and SARS CoV-2 surface proteins. Overall, increased levels of redox active metals and protein oxidation indicate that oxidative stress-induced protein oxidation in COVID-19 may be a consequence of the interactions of SARS-CoV-2 proteins with host cell metal binding proteins resulting in altered cellular homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%