A ratiometric two-photon fluorescent probe reveals reduction in mitochondrial H2S production in Parkinson's disease gene knockout astrocytes

Sung Keun Bae, Cheol Ho Heo, Dong Joo Choi, Debabrata Sen, Eun Hye Joe, Bong-Rae Cho, Hwan Myung Kim

Research output: Contribution to journalArticle

282 Citations (Scopus)

Abstract

Hydrogen sulfide (H2S) is a multifunctional signaling molecule that exerts neuroprotective effects in oxidative stress. In this article, we report a mitochondria-localized two-photon probe, SHS-M2, that can be excited by 750 nm femtosecond pulses and employed for ratiometric detection of H 2S in live astrocytes and living brain slices using two-photon microscopy (TPM). SHS-M2 shows bright two-photon-excited fluorescence and a marked change in emission color from blue to yellow in response to H 2S, low cytotoxicity, easy loading, and minimum interference from other biologically relevant species including reactive sulfur, oxygen, and nitrogen species, thereby allowing quantitative analysis of H2S levels. Molecular TPM imaging with SHS-M2 in astrocytes revealed that there is a correlation between the ratiometric analysis and expression levels of cystathionine β-synthase (CBS), the major enzyme that catalyzes H 2S production. In studies involving DJ-1, a Parkinson's disease (PD) gene, attenuated H2S production in comparison with wild-type controls was observed in DJ-1-knockout astrocytes and brain slices, where CBS expression was decreased. These findings demonstrate that reduced H2S levels in astrocytes may contribute to the development of PD and that SHS-M2 may be useful as a marker to detect a risk of neurodegenerative diseases, including PD.

Original languageEnglish
Pages (from-to)9915-9923
Number of pages9
JournalJournal of the American Chemical Society
Volume135
Issue number26
DOIs
Publication statusPublished - 2013 Jul 3

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Gene Knockout Techniques
Fluorescent Dyes
Photons
Astrocytes
Parkinson Disease
Genes
Microscopy
Brain
Microscopic examination
Cystathionine
Neurodegenerative diseases
Reactive Nitrogen Species
Hydrogen Sulfide
Mitochondria
Oxidative stress
Hydrogen sulfide
Neuroprotective Agents
Cytotoxicity
Ultrashort pulses
Sulfur

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

A ratiometric two-photon fluorescent probe reveals reduction in mitochondrial H2S production in Parkinson's disease gene knockout astrocytes. / Bae, Sung Keun; Heo, Cheol Ho; Choi, Dong Joo; Sen, Debabrata; Joe, Eun Hye; Cho, Bong-Rae; Kim, Hwan Myung.

In: Journal of the American Chemical Society, Vol. 135, No. 26, 03.07.2013, p. 9915-9923.

Research output: Contribution to journalArticle

Bae, Sung Keun ; Heo, Cheol Ho ; Choi, Dong Joo ; Sen, Debabrata ; Joe, Eun Hye ; Cho, Bong-Rae ; Kim, Hwan Myung. / A ratiometric two-photon fluorescent probe reveals reduction in mitochondrial H2S production in Parkinson's disease gene knockout astrocytes. In: Journal of the American Chemical Society. 2013 ; Vol. 135, No. 26. pp. 9915-9923.
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