Mechanism of Nitric Oxide Reactivity and Fluorescence Enhancement of the NO-Specific Probe CuFL1

McQuade, Lindsey E.; Pluth, Michael D.; Lippard, Stephen J.

doi:10.1021/ic101054u

Cited by 50 publications

(41 citation statements)

References 44 publications

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“…The Cu 2 ðFL2EÞ NO sensor was prepared as described (9,10). Polyclonal antibodies directed against phospho-eNOS (Ser1177), phospho-acetylCoA carboxylase (ACC) (Ser79), phospho-AMPK (Thr172), phospho-Akt (Ser473), phospho-MEK1/2 (Ser217/221), phospho-Erk1/2 (Thr202/Tyr204), ACC, AMPK, and Akt were from Cell Signaling Technologies.…”

Section: Methodsmentioning

confidence: 99%

Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis

Sartoretto

Kalwa

Pluth

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Nitric oxide (NO) and hydrogen peroxide (H 2 O 2 ) are synthesized within cardiac myocytes and play key roles in modulating cardiovascular signaling. Cardiac myocytes contain both the endothelial (eNOS) and neuronal (nNOS) NO synthases, but the differential roles of these NOS isoforms and the interplay of reactive oxygen species and reactive nitrogen species in cardiac signaling pathways are poorly understood. Using a recently developed NO chemical sensor [Cu 2 ðFL2EÞ] to study adult cardiac myocytes from wild-type, eNOS null , and nNOS null mice, we discovered that physiological concentrations of H 2 O 2 activate eNOS but not nNOS. H 2 O 2 -stimulated eNOS activation depends on phosphorylation of both the AMPactivated protein kinase and kinase Akt, and leads to the robust phosphorylation of eNOS. Cardiac myocytes isolated from mice infected with lentivirus expressing the recently developed H 2 O 2 biosensor HyPer2 show marked H 2 O 2 synthesis when stimulated by angiotensin II, but not following β-adrenergic receptor activation. We discovered that the angiotensin-II-promoted increase in cardiac myocyte contractility is dependent on H 2 O 2 , whereas β-adrenergic contractile responses occur independently of H 2 O 2 signaling. These studies establish differential roles for H 2 O 2 in control of cardiac contractility and receptor-dependent NOS activation in the heart, and they identify new points for modulation of NO signaling responses by oxidant stress.

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Section: Methodsmentioning

confidence: 99%

Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis

Sartoretto

Kalwa

Pluth

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…30 Although the CuBRNO probes are not completely selective, the fluorescent turn-on response of CuBRNO1 to HNO is significantly larger than for NO, and therefore this sensor might be useful for some cell imaging applications.…”

Section: Benzoresorufin-based Copper Complexes For Detection Of Hno Amentioning

confidence: 99%

Metal-Based Optical Probes for Live Cell Imaging of Nitroxyl (HNO)

Rivera‐Fuentes

Lippard

2015

Acc. Chem. Res.

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Conspectus: Nitroxyl (HNO) is a biological signaling agent that displays distinctive reactivity compared to nitric oxide (NO). As a consequence, these two reactive nitrogen species trigger different physiological responses. Selective detection of HNO over NO has been a challenge for chemists, and several fluorogenic molecular probes have been recently developed with that goal in mind. Common constructs take advantage of the HNO-induced reduction of Cu(II) to Cu(I).The sensing mechanism of such probes relies on the ability of the unpaired electron in a d orbital of the Cu(II) center to quench the fluorescence of a photoemissive ligand by either an electron or energy transfer mechanism. Experimental and theoretical mechanistic studies suggest that proton-coupled electron transfer mediates this process, and careful tuning of the copper coordination environment has led to sensors with optimized selectivity and kinetics.The current optical probes cover the visible and near-infrared regions of the spectrum. This palette of sensors comprises structurally and functionally diverse fluorophores such as coumarin 2 (blue/green emission), boron dipyrromethane (BODIPY, green emission), benzoresorufin (red emission), and dihydroxanthenes (near-infrared emission). Many of these sensors have been successfully applied to detect HNO production in live cells. For example, copper-based optical probes have been used to detect HNO production in live mammalian cells that have been treated with H 2 S and various nitrosating agents. These studies have established a link between HSNO, the smallest S-nitrosothiol, and HNO. In addition, a near-infrared HNO sensor has been used to perform multicolor/multianalyte microscopy, revealing that exogenously applied HNO elevates the concentration of intracellular mobile zinc. This mobilization of zinc ions is presumably a consequence of nitrosation of cysteine residues in zinc-chelating proteins such as metallothionein.Future challenges for the optical imaging of HNO include devising probes that can detect HNO reversibly, especially because ratiometric imaging can only report equilibrium concentrations when the sensing event is reversible. Another important aspect that needs to be addressed is the creation of probes that can sense HNO in specific subcellular locations. These tools would be useful to identify the organelles in which HNO is produced in mammalian cells and probe the intracellular signaling networks in which this reactive nitrogen species is involved. In addition, near-infrared emitting probes might be applied to detect HNO in thicker specimens, such as acute tissue slices and even live animals, enabling the investigation of the roles of HNO in physiological or pathological conditions in multicellular systems.

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“…, where L is a bidentate ligand such as dansyl ethylenediamine or dansyl aminomethylpyridine [145], or Cu [137], and an inner sphere mechanism in analogy to Scheme 8 was proposed [147].…”

Section: +mentioning

confidence: 99%

Mechanisms of Nitric Oxide Reactions Mediated by Biologically Relevant Metal Centers

Ford

Pereira

Miranda

2013

Nitrosyl Complexes in Inorganic Chemistry, Biochemistry and Medicine II

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Mechanism of Nitric Oxide Reactivity and Fluorescence Enhancement of the NO-Specific Probe CuFL1

Cited by 50 publications

References 44 publications

Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis

Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis

Metal-Based Optical Probes for Live Cell Imaging of Nitroxyl (HNO)

Mechanisms of Nitric Oxide Reactions Mediated by Biologically Relevant Metal Centers

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