Revelation of the dynamic progression of hypoxia-reoxygenation injury by visualization of the lysosomal hydrogen peroxide
- Department of Molecular and Cellular Pharmacology, Peking University School of Pharmaceutical Sciences, Beijing (China)
- Department of Medicinal Chemistry, Peking University School of Pharmaceutical Sciences, Beijing (China)
- Medical and Healthy Analysis Center, Peking University, Beijing (China)
Hydrogen peroxide (H{sub 2}O{sub 2}) plays an important role in pathological conditions, such as cerebral ischemia-reperfusion (I-R) injury. Fluorescent probes may serve as valuable tools to detect the amount, temporal and spatial distribution of H{sub 2}O{sub 2} in living cells. To investigate the role of lysosomal H{sub 2}O{sub 2} involved in cerebral I-R injury, we designed and synthesized a lysosome-targetable two-photon fluorescent probe ztl-4, through expansion and substitution of the original pyridazinone scaffold, conjugation of electronic-donating aromatic ring and precise terminal modification of the alkyl linker. The probe ztl-4 exhibited fast, sensitive and highly selective response toward H{sub 2}O{sub 2}. ztl-4 could image exogenous H{sub 2}O{sub 2} in SH-SY5Y cells and brain slices. In addition, ztl-4 was located in lysosomes with high colocalization coefficient compared with LysoTracker. ztl-4 was further applied for detecting the endogenous generation of H{sub 2}O{sub 2} in SH-SY5Y cells subjected to oxygen and glucose deprivation (OGD) or OGD/reoxygenation (OGD/R) injury. Both OGD- and OGD/R-induced cell injury caused a time-dependent increase of H{sub 2}O{sub 2} production within lysosomes. Moreover, OGD/R-treated cells showed much more amount of H{sub 2}O{sub 2} than OGD-treated cells, indicating that reoxygenation will promote H{sub 2}O{sub 2} accumulation in lysosomes of post-hypoxia cells. Therefore, the probe is suitable for monitoring the dynamic changes of lysosomal H{sub 2}O{sub 2} in cells. - Highlights: • New fluorescent probe displays high selectivity for H{sub 2}O{sub 2}. • The probe is lysosome-targetable. • The probe can real-time monitor hypoxia/reoxygenation injury-induced generation of H{sub 2}O{sub 2} in lysosomes of cells.
- OSTI ID:
- 22697007
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 486, Issue 4; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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