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Assessment of H₂S in vivo using the newly developed mitochondria-targeted mass spectrometry probe MitoA.

ABSTRACT: Hydrogen sulfide (H₂S) is produced endogenously in vivo and has multiple effects on signaling pathways and cell function. Mitochondria can be both an H₂S source and sink, and many of the biological effects of H₂S relate to its interactions with mitochondria. However, the significance of mitochondrial H₂S is uncertain, in part due to the difficulty of assessing changes in its concentration in vivo Although a number of fluorescent H₂S probes have been developed these are best suited to cells in culture and cannot be used in vivo To address this unmet need we have developed a mitochondria-targeted H₂S probe, MitoA, which can be used to assess relative changes in mitochondrial H₂S levels in vivo MitoA comprises a lipophilic triphenylphosphonium (TPP) cation coupled to an aryl azide. The TPP cation leads to the accumulation of MitoA inside mitochondria within tissues in vivo There, the aryl azido group reacts with H₂S to form an aryl amine (MitoN). The extent of conversion of MitoA to MitoN thus gives an indication of the levels of mitochondrial H₂S in vivo Both compounds can be detected sensitively by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the tissues, and quantified relative to deuterated internal standards. Here we describe the synthesis and characterization of MitoA and show that it can be used to assess changes in mitochondrial H₂S levels in vivo As a proof of principle we used MitoA to show that H₂S levels increase in vivo during myocardial ischemia.

SUBMITTER: Arndt S

PROVIDER: S-EPMC5427258 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Assessment of H2S in vivo using the newly developed mitochondria-targeted mass spectrometry probe MitoA.

Arndt Sabine S Baeza-Garza Carlos D CD Logan Angela A Rosa Tiziana T Wedmann Rudolf R Prime Tracy A TA Martin Jack L JL Saeb-Parsy Kourosh K Krieg Thomas T Filipovic Milos R MR Hartley Richard C RC Murphy Michael P MP

The Journal of biological chemistry 20170320 19

Hydrogen sulfide (H2S) is produced endogenously in vivo and has multiple effects on signaling pathways and cell function. Mitochondria can be both an H2S source and sink, and many of the biological effects of H2S relate to its interactions with mitochondria. However, the significance of mitochondrial H2S is uncertain, in part due to the difficulty of assessing changes in its concentration in vivo Although a number of fluorescent H2</ ...[more]

PMID: 28320864

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Dataset Information

Assessment of H₂S in vivo using the newly developed mitochondria-targeted mass spectrometry probe MitoA.

Publications

Assessment of H<sub>2</sub>S <i>in vivo</i> using the newly developed mitochondria-targeted mass spectrometry probe MitoA.

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