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Direct Assessment of Nitrative Stress in Lipid Environments: Applications of a Designer Lipid-Based Biosensor for Peroxynitrite

93 Pages Posted: 28 Aug 2023 Publication Status: Published

See all articles by Bryan Gutierrez

Bryan Gutierrez

Rutgers, The State University of New Jersey

Tushar Aggarwal

Rutgers, The State University of New Jersey

Huseyin Erguven

Rutgers, The State University of New Jersey

Rhia Stone

Rutgers, The State University of New Jersey

Changjiang Guo

Rutgers, The State University of New Jersey

Alyssa Bellomo

Rutgers, The State University of New Jersey

Elena Abramova

Rutgers, The State University of New Jersey

Emily Stevenson

Rutgers, The State University of New Jersey

Andrew Gow

Rutgers, The State University of New Jersey

Enver Cagri Izgu

Rutgers, The State University of New Jersey

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Abstract

Lipid membranes and lipid-rich organelles are targets of peroxynitrite (ONOO–), a highly reactive species generated under nitrative stress. We report a membrane-localized phospholipid (DPPC-TC-ONOO–) that allows the detection of ONOO– in diverse lipid environments: biomimetic vesicles, mammalian cell compartments, and within the lung lining. DPPC-TC-ONOO– and POPC self-assemble to membrane vesicles that fluorogenically and selectively respond to ONOO–. DPPC-TC-ONOO–, delivered through lipid nanoparticles, allowed for ONOO– detection in the endoplasmic reticulum upon cytokine-induced nitrative stress in live mammalian cells. It also responded to ONOO– within lung tissue murine models upon acute lung injury. We observed nitrative stress around bronchioles in precision cut lung slices exposed to nitrogen mustard and in pulmonary macrophages following intratracheal bleomycin challenge. Results showed that DPPC-TC-ONOO– functions specifically toward iNOS, a key enzyme modulating nitrative stress, and offers significant advantages over its non-amphiphilic analog in terms of localization and signal generation.

Keywords: Nitrative stress, peroxynitrite, membrane, iNOS, biosensing, live cell imaging, inflammatory response, acute lung injury

Suggested Citation

Gutierrez, Bryan and Aggarwal, Tushar and Erguven, Huseyin and Stone, Rhia and Guo, Changjiang and Bellomo, Alyssa and Abramova, Elena and Stevenson, Emily and Gow, Andrew and Izgu, Enver Cagri, Direct Assessment of Nitrative Stress in Lipid Environments: Applications of a Designer Lipid-Based Biosensor for Peroxynitrite. Available at SSRN: https://ssrn.com/abstract=4549880 or http://dx.doi.org/10.2139/ssrn.4549880
This version of the paper has not been formally peer reviewed.

Bryan Gutierrez

Rutgers, The State University of New Jersey ( email )

Tushar Aggarwal

Rutgers, The State University of New Jersey ( email )

Huseyin Erguven

Rutgers, The State University of New Jersey ( email )

Rhia Stone

Rutgers, The State University of New Jersey ( email )

Changjiang Guo

Rutgers, The State University of New Jersey ( email )

Alyssa Bellomo

Rutgers, The State University of New Jersey ( email )

Elena Abramova

Rutgers, The State University of New Jersey ( email )

Emily Stevenson

Rutgers, The State University of New Jersey ( email )

Andrew Gow

Rutgers, The State University of New Jersey ( email )

Enver Cagri Izgu (Contact Author)

Rutgers, The State University of New Jersey ( email )

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