Imaging Hg2+-Induced Oxidative Stress by NIR Molecular Probe with "dual-Key-and-Lock" Strategy

Article abstract of DOI:10.1021/acs.analchem.0c02509

Mercury (Hg) is considered an extremely toxic heavy metal which is extremely harmful to both the human body and environment. In addition, Hg2+-induced oxidative stress also exerts a crucial role to play in pathophysiological mechanisms of mercury toxicity

Full text of DOI:10.1021/acs.analchem.0c02509

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Article
Imaging Hg2+-induced oxidative stress by NIR
molecular probe with “dual-key-and-lock” strategy
Xiaopeng Yang, xiaojing han, yongru zhang, jianfei liu, Jun Tang, Di Zhang, yufen zhao, and Yong Ye
Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.0c02509 • Publication Date (Web): 31 Jul 2020
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Analytical Chemistry
2
+
Imaging Hg -induced oxidative stress by NIR molecular
probe with “dual-key-and-lock” strategy
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a
a
a
a
a
b, *
a, c
Xiaopeng Yang , Xiaojing Han , Yongru Zhang , Jianfei Liu , Jun Tang , Di Zhang , Yufen Zhao ,
a,*
Yong Ye
a
Green Catalysis Center, and College of Chemistry, Zhengzhou University, Zhengzhou 450001, China. *Corresponding
author, E-mail: yeyong03@tsinghua.org.cn
b
Institute of Agricultural Quality Standards and Testing Technology, Henan Academy of Agricultural Sciences, Zhengzhou
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50002, China. E-mail: pandy811@163.com
c
Institute Drug Discovery Technology, Ningbo University, Ningbo 315211, Zhejiang, China
ABSTRACT: Mercury (Hg) is considered as an extremely toxic heavy metal which is extremely harmful to both the human body
and environment. In addition, Hg -induced oxidative stress also exerts a crucial role to play in pathophysiological mechanisms of
mercury toxicity. Thus, the efficient and specific fluorescent probes for imaging Hg -oxidative stress are necessary. In the present
study, we rationally design a novel Hg -activated and ICT-based NIR emission fluorescent probe NIR-HO for sequentially
monitoring ONOO level with “dual-key-and-lock” strategy. The probe NIR-HO showed rapid response, excellent specificity and
sensitivity for the detection of Hg and ONOO in vitro. Cells imaging demonstrated that Hg -induced oxidative stress was
involved in ONOO upregulation. Besides, GSH, NAC and EDTA were employed as excellent detoxifying drug against Hg -
induced toxicity. Moreover, the probe NIR-HO was successfully used for imaging Hg and ONOO in vivo. In brief, NIR-HO
2+
2+
2+
−
2
+
−
2+
−
2+
2
+
−
2
+
provides a simple and powerful approach which can be used to image Hg -induced oxidative stress in the pathological
environment.
Introduction
fluorescent probes have been extremely employed to reveal the
physiological activities of metal ions, anions, enzyme, ROS, RSS
2
9-36
It is acknowledged that mercury (Hg) is a highly poisonous
heavy metal, which has been considered as the major threat to
human health. Hg is usually transferred into the human body
through the food chain and deposited, and then cause chronic
poisoning which has been proven to lead to liver, kidneys, brain,
stomach and nerve damage.
and RNS.
In particular, near-infrared (NIR) emission at 650-
900 nm fluorescent probes have advantages associated with
maximizing tissue penetration, avoiding biological background
fluorescence and less damage, and consequently have attracted
extensive attention of chemist.
many of fluorescent probes have been reported.
most of probes for Hg and ONOO are developed based on
“one-key-and-lock” strategy whose fluorescent signals are
switched on by one “key” Hg or ONOO (Scheme 1A).
Designing a probe, whose emission can only be switched on in the
presence of two “keys” Hg and ONOO , is better for
specifically studying the process of Hg -induced ONOO
1
37-43
−
2+
To detect ONOO or Hg ,
2
-4
44-51
Nevertheless, the relevant
However,
2
+
2+
−
pathogenesis of Hg chronic poisoning has not been clear.
2
+
Recently, Hg was dementated to show a strong affinity for the
mercapto (SH)-containing complexes in human body, which can
cause the sulfhydryl groups of proteins, enzymes and lipids to
2
+
−
52-59
5
,
6
2+
−
agglomerate.
Besides, the explosion of ROS caused by
2+
−
oxidative stress may be closely associated with mercury-induced
7
,
8
2+
60-63
toxicity.
leads to NO and O
antioxidants in the body by connecting with the mercapto (-SH)
Increasing intracellular Hg concentrations usually
generation with “dual-key-and-lock” strategy
developing a simple, NIR-emission and powerful molecular probe
for meeting the needs of monitoring Hg and ONOO is
necessary to study.
. As a result,
·−
2
bursting as well as deactivate the
2
+
−
·
−
group. O
2
reacts rapidly with NO to generate peroxynitrite
−
9
10-16
(ONOO ). In life system, as strong oxidant and nucleophile
,
2+
−
To realize the visual imaging of Hg -induced ONOO
generation, we designed and synthesized a novel Hg -activated
and near-infrared emission fluorescent probe NIR-HO based on
ICT for detecting Hg and ONOO with “dual-key-and-lock”
strategy and “AND” logic gate (Scheme 1B, C). The
diphenylphosphinothioyl moiety was introduced into NIR
emission fluorophore to achieve high efficiency, sensitivity and
selectivity detection of Hg and ONOO . At first, the P=S of
thiophosphinate was oxidized by Hg to P=O; Then ONOO
would promote cleavage of the phosphinate ester P–O bond in
NIR-Hg to produce NIR-ONOO.
broken by ONOO , the NIR emission enhanced. In addition, the
probe was proved to be highly selective for monitoring Hg and
ONOO in the biological system. More importantly, we found that
Hg can cause oxidative stress and generate peroxynitrite
(ONOO ) from cell imaging for the first time. These results might
provide a guiding significance to deeply study the pathological
mechanisms of Hg-induced diseases and death.
2
+
−
Hg -induced ONOO can directly interact with proteins, lipids,
DNA by oxidation, and can also be converted to other ROS
including hydroxyl radicals, carbonate radicals, and nitrogen
2+
2+
−
1
7-19
−
dioxide.
Actually, mis-regulation of ONOO levels often
causes various diseases including stroke, heart disease,
neurodegenerative disease, cardiovascular disease, inflammation
and cancer.
caused by Hg -induced oxidative stress still remain unclear due
to its short life, highly active, and low level. Moreover, the
precise mechanism of Hg and ONOO in the biological
environment is not completely known.
of efficient methods and technologies to monitor the Hg -
induced oxidative stress would be conductive to deeply
understanding the biological role of Hg -induced diseases.
2
0-25
−
However, abnormal changes of ONOO level
2+
−
2
+
2+
−
26
2+
−
3, 64-66
When the P–O bond was
2
7, 28
Thus, the development
−
2
+
2+
−
2
+
2+
−
Due to its low cost, low radioactivity, high sensitivity and
rapidly catch information of activated species in the biological
environment in combination with fluorescent imaging technology,
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Scheme 1. A) Design strategy of previous probes; B) The truth table of NIR-HO; C) Response mechanism of probe NIR-HO.
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Experimental
Leica TCS SP8 confocal microscope. (excitation: 552 nm
emission: 640-720 nm)
Synthesis. Intermediates compounds 1 and 2 were synthesized
based on published procedures
Mice imaging. Before imaging, the Kunming mice were fasted
for 12 hours to avoid possible food fluorescence interference to
the dye fluorescence. The mice were classified into two groups.
The first group was given an injection of NIR-HO (10 μM, 100
μL) for 0.5 hour and then given an injection of PBS (100 μL) and
was imaged after 0.5 hour. Followed by subcutaneously injection
6
7, 68
.
Preparation of NIR-HO: Compound 2 (290.4 mg, 1 mmol) was
dissolved in THF (10 ml) with triethylamine (152.0 mg, 1.5
mmol), and then compound 1 (379.0 mg, 1.5mmol) was added at
o
0
C, and stirred 12 hours at room temperature. Then removing
2+
−
THF by evaporation, the remaining solid was purified by silica
column chromatography and recrystallization to provide a yellow
solid 435.7 mg NIR-HO with 86% yield. H NMR (CDCl
with Hg and ONOO (100 μL, 10 μM), the second group was
given an injection of NIR-HO (10 μM, 100 μL) for 0.5 hour, and
was imaged after 0.5 hour. Before imaging, the mice were
anesthetized with 4% chloral hydrate (15 mL/kg) by
intraperitoneal injection. Then, whole body images of the mice
were acquired using an IVIS Lumina III system with channel
(560-nm excitation and 670-nm emission).
1
3
, 400
MHz):  = 8.01 (m, 4H), 7.55 (m, 6H), 7.41 (d, J = 8.6 Hz, 2H),
7
.10 (m, 2H), 7.00 (d, J = 16.1 Hz, 1H), 6.88 (d, J = 16.1 Hz, 1H),
1
3
6
.82 (s, 1H), 2.61 (s, 2H), 2.45 (s, 2H), 1.09 (s, 6H) ppm;
, 100 MHz):  =169.3, 153.7, 151.7 (J = 8.8 Hz),
36.0, 134.0 (J = 110.2 Hz), 132.4 (J = 4.6 Hz), 131.4 (J = 11.6
Hz), 128.9, 128.7, 128.6 (J = 13.6 Hz), 123.5, 122.4 (J = 5.1 Hz),
C
NMR (CDCl
3
1
Scheme 2. Synthetic route of probe NIR-HO.
3
1
113.1 (J = 78.2 Hz), 78.7, 43.0, 39.2, 32.0, 28.0 ppm; P NMR
(162ꢀMHz, CDCl
calcd for [C31H N OPS] =507.1654, Found: 507.1654.
o
3
):  = 82.8 ppm; Mp: 201-202 C; HR-MS: m/z
+
27 2
Cytotoxicity assays. Cytotoxicity assays were performed by
using Cell Counting Kit-8 (CCK-8) in accordance with our
previously reported. The cells were treated with probe NIR-HO
(0-20 μM) for 24 hours, and the cell cytotoxicity was determined
by CCK-8 analysis.
Cell Culture and Imaging. MCF-7 cells were cultured in
RPMI-1640 supplemented with 10% fetal bovine serum, at 37.0
°
2
C, in 5% CO . Cells were plated on culture dish and allowed to
adhere for 24 hour. Before carrying out the experiments, the
media was removed and the cells were washed three times with
PBS buffer (pH 7.4). Cells were imaged with the application of
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−
Figure 1. A) The absorption spectra. B) Fluorescence emission spectra of NIR-HO (10 µM) toward Hg and ONOO (10 equiv.). C)
2
+
−
Time-dependent intensity at 680 nm of NIR-HO (10.0 µM) to Hg and ONOO (10 equiv.). D) Fluorescence titrations spectra of NIR-HO
−
2+
o
(
10.0 µM) toward ONOO in the presence of 10 equiv. Hg . (PBS/EtOH=4/6, v/v, 10 mM, pH 7.4, 25 C, Ex = 550 nm)
time, two new absorptions at 440 and 550 nm appeared (Figure
Results and discussion
1B). The time dependence of the emission profile of was
measured via recording changes in emission at 680 nm towards
Design and Synthesis of NIR-HO. In order to achieve specific
2
+
−
Hg and ONOO . Obviously, no obvious change of fluorescence
2+
detection of Hg -induced oxidative stress, it is urgently needed to
2
+
emission intensity could be found after the addition of Hg or
ONOO within 5 minutes (Figure 1C). However, the emission
2
+
−
develop an efficient tool for Hg and ONOO combined
detection. We choose “dual-key-and-lock” strategy to apply for
probe designing. The thiophosphinate ester moiety can be used as
a “lock” with two “keys” Hg and ONOO . Meanwhile, near-
infrared emission fluorophore serves as the reporting signal part.
Furthermore, probe NIR-HO can be easily synthesized in a few
steps as depicted in Scheme 2. The NMR and HR-MS
spectroscopy of probe NIR-HO were shown in supplementary
data (Figure S1-4).
−
showed significant enhancement and reached maximum plateau
2+
value within 5 minutes after simultaneously adding Hg and
2
+
−
−
ONOO . As shown in Figure 1D, We further investigated the
fluorescent titration experiment. At first, we added 10 equiv. of
2
+
Hg to solution for activating NIR-HO, and the fluorescence
emission intensity was gradually enhanced and rose to platform
−
emission intensity with different concentration ONOO 0-100
µM. According to Figure S5, the emission intensity (680 nm)
Spectroscopic response of NIR-HO. When obtaining the
designed probe, we studied the sensing ability of NIR-HO (10
−
2
indicated a good linear relationship to ONOO concentration (R
=
−
0.9974). Afterwards, the limit of detecting for ONOO was 24.0
2
+
−
2
µM) towards Hg and ONOO in PBS buffer (H O/EtOH=4/6,
nM according to the 3σ/slope. Clearly, the obtained results
demonstrated that probe NIR-HO performed excellent sensitivity,
v/v) at first. Probe NIR-HO (Φ = 0.01) presented weakly
fluorescence emission at 680 nm and absorption center at 410 nm
from fluorescence emission and absorption spectra (Figure 1A,
B). With only 10 equiv. of Hg added, the emission showed a
negligible change, and the absorption center shifted to 420 nm.
Moreover, there also existed no change of fluorescence responses
2+
effectiveness and potential applications for detection of Hg -
−
induced ONOO generation. To examine the practical
2+
applicability NIR-HO in different pH PBS buffer, the
2+
−
fluorescence response of NIR-HO toward Hg and ONOO at
different pH was explored (Figure S6). The probe NIR-HO
showed faint and stabile fluorescence emission with different pH,
−
and absorption after only addition of 10 equiv. ONOO . When
2
+
−
both Hg and ONOO were added, the fluorescence intensity
−
even if mercury ions and ONOO were added separately. While
gradually increased to a quantum yield of Φ = 0.16. At the same
2+
−
upon addition of both Hg and ONOO , fluorescence emission
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Figure 2. A) The fluorescence emission spectra of NIR-HO (10 µM) responded to other analytes (10 equiv.) in the presence of 10 equiv.
Hg . B) The fluorescence emission spectra of probe NIR-HO (10 µM) responded to 10 equiv. ONOO in the presence of 10 equiv. other
metal ions. (Ex = 550 nm)
2
+
−
Figure 3. Fluorescence images of NIR-HO towards Hg2+ and ONOO in MCF-7 cells. (a1-3) treated with NIR-HO (10 μM, 0.5 hour).
−
2
+
(b1-3) pretreated with NIR-HO (10 μM, 0.5 hour) then incubated with Hg (10 μM, 0.5 hour). (c1-3) treated with NIR-HO (10 μM, 0.5
−
2+
hour) then incubated with ONOO (100 μM, 0.5 hour). (d1-4) pretreated with NIR-HO (10 μM, 0.5 hour), then incubated with Hg (100
−
μM) and ONOO (100 μM) for 0.5 hour. (e1-3) pretreated with (LPS) and IFN-γ for 24 hour, then treated with NIR-HO (10 μM) for 0.5
hour. (a3-e3) Merged images of a1-e1 and a2-e2. (Excitation: 552 nm, emission: 640-720 nm, Scale bar: 50 μm).
·−
−
2 2 2
H O , TBHP, ·OH, O , ClO ), Figure 2B also presented no
obvious change of fluorescence emission intensity. With this just
intensity was significantly increased across a range of pH from
.0 to 12.0, suggesting that the probe NIR-HO can be applied to
physiological environment.
the opposite is, probe NIR-HO only opened strong fluorescence
6
2+
−
emission after the addition of both Hg and ONOO . The
−
competitive binding assay revealed that the ONOO induced
To test the selectivity and specificity of probe NIR-HO in
complex biological system. The probe NIR-HO was firstly treated
fluorescence response was not affected by other interferences
(
Figure S7). Additionally, the influence of biologically relevant
−
+
2+
+
with various potentially activated species (ClO , K , Ca , Na ,
2
+
species on the UV performance of probe NIR-HO toward Hg
and ONOO was also discussed (Figure S8). It can be found that
biologically relevant species showed negligible interference for
2+
3+
3+
2+
2+
+
2+
2+
2+
2+
Mg , Al , Fe , Pb , Cu , Ag , Cd , Fe , Zn , Ni ) and
ONOO . As illustrated in Figure 2A, there was no significantly
−
−
fluorescence emission changed at 680 nm. Similarly, upon treated
2+
−
the detection of Hg and ONOO . These preliminary results
2
+
−
−
−
−
with Hg and other biologically relevant species (F , Cl , Br , I ,
−
2−
2−
−
−
AcO , CO
3 3 3 2
, SO , GSH, Hcy, Cys, NO , NO , NO, HNO,
1
2
O ,
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Figure 4. Fluorescence images of Hg -induced oxidative stress with probe NIR-HO in MCF-7 cells. (a-d) Cells treated with different
2
+
concentration of Hg (0, 50, 100, 200 μM) for 1 hour, followed treatment with NIR-HO (10 μM) for 0.5 hour. (a3-d3) Merged images of
a1-d1 and a2-d2. (Excitation: 552 nm, emission: 640-720 nm, Scale bar: 50 μm).
2
+
2+
Figure 5. Fluorescence images of NIR-HO for Hg -induced oxidative stress in MCF-7 cells. (a1-a3) cells with Hg (200 μM) for 1 hour,
2
+
subsequently treated with NIR-HO (10 μM, 0.5 hour). (b1-b3) cells were pretreated with NAC (1.0 mM, 1 h), then exposed to Hg (200
μM), treatment with NIR-HO (10 μM, 0.5 hour); (c1-c3) pretreated with GSH (1.0 mM, 1 h), then exposed to Hg (200 μM), treatment
with NIR-HO (10 μM, 0.5 hour); (d1-d3) pretreated with EDTA (1.0 mM, 1 h), then exposed to Hg (200 μM), treatment with NIR-HO
2
+
2
+
(10 μM, 0.5 hour); (a3-d3) Merged images of a1-d1 and a2-d2. (Excitation: 552 nm, emission: 640-720 nm, Scale bar: 50 μm).
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indicated high specificity and selectivity of NIR-HO to detect
Hg and ONOO with “dual-key-and-lock” strategy.
The toxicity of mercury ions shows a major threat to human
2
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−
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health. Therefore, it is of great significance to find mercury
detoxification drugs. Accordingly, GSH and NAC may effectively
Sensing mechanism. The possible recognition process was
shown in Scheme 1, and the P=S of probe NIR-HO was firstly
2
+
combined with Hg to reduce its concentration, and deplete ROS
and RNS levels in cells. EDTA is a good mercury ion chelator,
2
+
oxidized to P=O by Hg because of its strong oxidation. The
2
+
which may efficiently induce decrease of Hg level in cells.
intermediate product NIR-Hg (calcd m/z 513.1702,
2+
+
Therefore, in order to protect the cells from Hg damage, we
C
31
H
27
N
2
NaO
2
P ) was found in the HR-MS spectrum with a peak
attempt to use NAC, GSH and EDTA as mercury detoxification
at m/z 513.1714 (Figure S9). Subsequently, the P-O of NIR-Hg
2
+
−
drug based on the Hg -induced toxicity mechanism. As shown in
was broken by ONOO , which generated the obvious fluorescence
Figure 5a, NIR-HO loaded cells showed enhanced fluorescence
emission of NIR-ONOO. The founded peaks at m/z 289.1348
2
+
-
signal after stimulated with Hg . However, upon stimulation of
these drugs NAC, GSH and EDTA, intracellular fluorescence
signal in cells gradually decreased (Figure 5b-d). As a result, the
results confirmed that NAC, GSH and EDTA can be potentially
(C19
H
17
N
2
O ) belonged to NIR-ONOO (calcd m/z 289.1346)
2
+
0
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0
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(Figure S10). Generally, due to the series reaction of Hg and
−
ONOO with the probe NIR-HO, the ICT system was then
enhanced and released strong fluorescence signal, suggesting that
probe NIR-HO was designed in line with “dual-key-and-lock”
strategy.
2+
employed as a detoxifying drugs for remedy Hg -induced
toxicity.
In vivo imaging. Finally, we further investigated the feasibility
Cell imaging. Inspired by the exceptional spectrum results of
2
+
−
of NIR-HO for visualizing Hg and ONOO in Kunming mice
motivated by its NIR fluorescence emission. Based on Figure 6,
the mice displayed faint fluorescence emission in NIR emission
channel which was subcutaneously injected with only NIR-HO.
In another group, obvious fluorescence emission enhancement
was observed after given a subcutaneous injection of NIR-HO,
probe (Figure S11-12), we continued to investigate the application
2+
−
of NIR-HO toward Hg
and ONOO in the biological
environment. We first evaluated the cytotoxicity of NIR-HO
using MCF-7 cells. The cell cytotoxicity was calculated by CCK-
analysis through treating cells with NIR-HO (0-20 μM) for 24
hours. Those results indicated that cell viability had remained
0% after incubation of cells for 24 hours, as shown in Figure
8
2+
−
then an injection of Hg and ONOO stock solution 0.5 hour
9
later. Therefore, this suggested that NIR-HO can be applied to
S13, demonstrating that NIR-HO has low cytotoxicity for cell
imaging.
2
+
−
image Hg and ONOO in vivo.
Subsequently, cells which were first incubated with NIR-HO
showed a negligible fluorescence signal (Figure 3a). Upon treated
2
+
with Hg , cells revealed a little fluorescence enhancement due to
2
+
−
Hg -induced ONOO generation (Figure 3b). When cells were
−
treated with ONOO , negligible fluorescence signal was existed
(
Figure 3c). In sharp contrast, when cells were incubated with
2
+
−
Hg and ONOO , a significant fluorescence increase could be
observed (Figure 3d), indicating that simultaneous stimulation of
2+
−
Hg and ONOO on the probe can contribute to fluorescence
signal increase. After addition of LPS and IFN-γ for 24 hours,
−
cells can endogenously generate ONOO . Then, cultured with
NIR-HO for another 0.5 hour, cells showed a negligible change
of fluorescence (Figure 3e). The results showed that NIR-HO can
2
+
−
respond to Hg and ONOO with excellent selectivity and
sensitivity in cells, and did not respond to other processes which
induced oxidative stress in cells.
Normally, Hg belongs to one of the most toxic heavy metals,
which can cause kidney, liver and nervous system poisoning.
Although, lots of studies have been conducted on Hg-induced
toxicity, its mechanism has not been fully elucidated. Oxidative
stress may be closely related to Hg-induced toxicity. Therefore,
2
+
Hg -induced oxidative stress was real-time monitoring in cells by
2
+
−
using the NIR-HO for Hg and ONOO detection. As presented
in Figure 4a-d, cells incubated with NIR-HO, weak
a
fluorescence signal could be observed. As our expectation, when
Figure 6. Fluorescent images of NIR-HO in vivo. Left: Mice
were injected with NIR-HO (100 μL, 10 μM) for 0.5 hour,
subcutaneously injected PBS buffer (100 μL left), then imaged.
2+
cells were exposed to increasing concentrations of Hg , displayed
significant fluorescent signal increasing. In order to study if NIR-
−
2+
2+
−
HO dynamically monitoring the production of ONOO by Hg -
induced oxidative stress, we recorded fluorescence signal changes
at different time points. Cells were first cultured with the NIR-
HO, then imaged. As the Figure S14 shows, fluorescence signal
of cells did not change significantly which were incubated with
Right: mice were injected Hg and ONOO (100 μL, 10 μM) for
0.5 hour, then imaged. (550-nm excitation and 680-nm emission).
CONCLUSIONS
To conclude, we have reported a new type of Hg -activated and
NIR emission fluorescent probe NIR-HO for detecting ONOO
2+
PBS only. However, when Hg was used to stimulate cells, a
2
+
fluorescence intensity augmentation was observed in a short
−
−
period of time, indicating that ONOO - related oxidative stress
2
+
with “dual-key-and-lock” strategy. The probe NIR-HO showed
showed up after Hg administration. Consequently, the results
2+
excellent specificity and sensitivity for detecting Hg and
demonstrated that NIR-HO can be appropriate for monitoring
−
2+
2
+
ONOO in vitro and cells. In addition, it was proved that Hg
Hg -induced oxidative stress in living cells.
could damage the body's antioxidant defense system function,
−
causing the occurrence of ONOO level upregulation. Therefore,
ACS Paragon Plus Environment

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Analytical Chemistry
oxidative stress may be the main pathogenic mechanism in
mercury-induced toxicity. More importantly, it was found that
NAC, GSH, and EDTA were employed as an excellent
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ASSOCIATED CONTENT
Supporting Information
The details of apparatus, materials, H NMR, 13C NMR, and HR-
MS spectra; fluorescent and UV spectroscopic data, cytotoxicity
assay, bioimaging could be found in supporting information,
which is available free of charge on the ACS Publications
website.
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(13). Tsai, J.-H. M.; Harrison, J. G.; Martin, J. C.; Hamilton, T. P.; van der
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AUTHOR INFORMATION
Corresponding Author
Inhibition of arginase by in alveolar macrophages: implications for the
utilization of l-arginine for nitric oxide synthesis. FEBS Lett. 1995, 359
(2-3), 251-254.
*
E-mail: yeyong03@tsinghua.org.cn. Tel: +86-371-67767050.
(16). Hey, C.; Boucher, J. L.; Goff, F. V. L.; Ketterer, G.; Wessler, I.;
Racke, K., Inhibition of arginase in rat and rabbit alveolar macrophages by
N-omega-hydroxy-D,L-indospicine, effects on L-arginine utilization by
nitric oxide synthase. Br. J. Pharmacol. 1997, 121, 395-400.
Fax: +86-371-67767051. pandy811@163.com
ORCID
(17). Ferrer-Sueta, G.; Campolo, N.; Trujillo, M.; Bartesaghi, S.;
Yong Ye: 0000-0001-6234-3971
Carballal, S.; Romero, N.; Alvarez, B.; Radi, R., Biochemistry of
Peroxynitrite and Protein Tyrosine Nitration. Chem. Rev. 2018, 118, 1338-
1408.
(18). Cheng, J.; Li, D.; Sun, M.; Wang, Y.; Xu, Q.-Q.; Liang, X.-G.; Lu,
Y.-B.; Hu, Y.; Han, F.; Li, X., Physicochemical-property guided design of
a highly sensitive probe to image nitrosative stress in the pathology of
stroke. Chem.l Sci. 2020, 11, 281-289.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
(19). Radi, R., Oxygen radicals, nitric oxide, and peroxynitrite: Redox
This work was financially supported by the National Science
Foundation of China (No. 21572209 and 21907025), Scientific
and Technological Project of Henan Province of China
pathways in molecular medicine. Proc. Natl. Acad. Sci. U. S. A. 2018,
115, 5839-5848.
(20). Cheng, D.; Pan, Y.; Wang, L.; Zeng, Z.; Yuan, L.; Zhang, X.; Chang,
Y.-T., Selective Visualization of the Endogenous Peroxynitrite in an
(192102310140), Scientific and Technological Innovation Project
Inflamed Mouse Model by
a Mitochondria-Targetable Two-Photon
of Henan Academy of Agricultural Sciences(2020CX05)
Ratiometric Fluorescent Probe. J. Am. Chem. Soc.2017, 139, 285-292.
(21). Huang, J.; Li, J.; Lyu, Y.; Miao, Q.; Pu, K., Molecular optical
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Nat. Mater. 2019, 18, 1133-1143.
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