Nox2 redox signaling maintains essential cell populations in the brain

Dickinson, Bryan C.; Peltier, Joseph; Stone, Daniel; Schaffer, David V.; Chang, Christopher J.

doi:10.1038/nchembio.497

Cited by 247 publications

(242 citation statements)

References 50 publications

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“…By contrast, EEPF1 is esterified with a truncated PEG (see Scheme 1) so would be expected to possess a higher capacity for intracellular penetration. Furthermore, hydrolysis of the PEG ester by intracellular esterases may enhance cellular retention of the active species, as reported for a similar aryl boronate probe, PF6-AM [33].…”

Section: Hnementioning

confidence: 61%

Boronate probes for the detection of hydrogen peroxide release from human spermatozoa

Purdey

Connaughton

Whiting

et al. 2015

Free Radical Biology and Medicine

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Section: Hnementioning

confidence: 61%

Boronate probes for the detection of hydrogen peroxide release from human spermatozoa

Purdey

Connaughton

Whiting

et al. 2015

Free Radical Biology and Medicine

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“…In vitro methods to interrogate redox chemistry have relied on designer redox-sensitive fluorescent proteins (yellow-or green fluorescent protein) incorporating an artificial dithiol-disulfide pair (28), or on detection of ROS themselves via chemical switching (29). In general, fluorescent probes have limited clinical translation given poor tissue penetration; making MR-compatible hyperpolarized 13 C probes an attractive alternative.…”

Section: Resultsmentioning

confidence: 99%

“…Alterations in cellular redox are implicated in a large number of pathologic processes, with a growing body of evidence also suggesting that controlled ROS chemistry is essential for normal development (29). Given the universality of redox chemistry in the functional cell, we developed hyperpolarized [1-13 C] DHA, a MR-compatible endogenous probe to interrogate populations of key redox pairs in vivo, in particular GSH/ GSSG that are coupled to intracellular DHA reduction.…”

Section: Discussionmentioning

confidence: 99%

Hyperpolarized ¹³ C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging

Keshari

Kurhanewicz

Bok

et al. 2011

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

149

159

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Reduction and oxidation (redox) chemistry is involved in both normal and abnormal cellular function, in processes as diverse as circadian rhythms and neurotransmission. Intracellular redox is maintained by coupled reactions involving NADPH, glutathione (GSH), and vitamin C, as well as their corresponding oxidized counterparts. In addition to functioning as enzyme cofactors, these reducing agents have a critical role in dealing with reactive oxygen species (ROS), the toxic products of oxidative metabolism seen as culprits in aging, neurodegenerative disease, and ischemia/ reperfusion injury. Despite this strong relationship between redox and human disease, methods to interrogate a redox pair in vivo are limited. Here we report the development of [1-13 C] dehydroascorbate [DHA], the oxidized form of Vitamin C, as an endogenous redox sensor for in vivo imaging using hyperpolarized 13 C spectroscopy. In murine models, hyperpolarized [1-13 C] DHA was rapidly converted to [1-13 C] vitamin C within the liver, kidneys, and brain, as well as within tumor in a transgenic prostate cancer mouse. This result is consistent with what has been previously described for the DHA/Vitamin C redox pair, and points to a role for hyperpolarized [1-13 C] DHA in characterizing the concentrations of key intracellular reducing agents, including GSH. More broadly, these findings suggest a prognostic role for this new redox sensor in determining vulnerability of both normal and abnormal tissues to ROS.MRI | molecular imaging | probe | kinetics

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“…Newer generation "non-redox" fluorescent probes are now being developed which exhibit greater stability and cellular localization in living cells (27,(41)(42)(43). One such probe is mitochondria peroxy yellow 1 (Mito-PY1) (41), which colocalizes with Mitotracker deep red and was used to assess H 2 O 2 levels in isolated mTAL epithelial cells (142) .…”

Section: Consequences Of Increased Mtal Luminal Flow and Namentioning

confidence: 99%

Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

Cowley

Abe

Mori

et al. 2015

American Journal of Physiology-Renal Physiology

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logical evidence linking the production of superoxide, hydrogen peroxide, and nitric oxide in the renal medullary thick ascending limb of Henle (mTAL) to regulation of medullary blood flow, sodium homeostasis, and long-term control of blood pressure is summarized in this review. Data obtained largely from rats indicate that experimentally induced elevations of either superoxide or hydrogen peroxide in the renal medulla result in reduction of medullary blood flow, enhanced Na ϩ reabsorption, and hypertension. A shift in the redox balance between nitric oxide and reactive oxygen species (ROS) is found to occur naturally in the Dahl salt-sensitive (SS) rat model, where selective reduction of ROS production in the renal medulla reduces salt-induced hypertension. Excess medullary production of ROS in SS rats emanates from the medullary thick ascending limbs of Henle [from both the mitochondria and membrane NAD(P)H oxidases] in response to increased delivery and reabsorption of excess sodium and water. There is evidence that ROS and perhaps other mediators such as ATP diffuse from the mTAL to surrounding vasa recta capillaries, resulting in medullary ischemia, which thereby contributes to hypertension.superoxide (O 2 ·Ϫ ); hydrogen peroxide (H2O2); nitric oxide (NO); NAD(P)H oxidase; mTAL; medullary blood flow; kidney; Dahl SS rats REACTIVE OXYGEN SPECIES (ROS) are chemically reactive molecules derived from oxygen, whose role as mediators of intracellular signaling cascades is well recognized. The following is a brief review of physiological data linking superoxide (O 2 ·Ϫ ), hydrogen peroxide (H 2 O 2 ), and nitric oxide (NO) production in the medullary thick ascending limbs of Henle (mTAL) to sodium (Na ϩ ) homeostasis, the regulation of medullary blood flow (MBF), and the long-term regulation of arterial blood pressure. MBF to the renal medulla can be importantly controlled by the constriction and dilation of the descending vasa recta (VR) capillaries, which branch from the efferent arterioles of the juxtamedullary glomeruli (49, 147, 149) and whose tone is controlled by the smooth muscle-like pericytes (49, 90, 146 -149). The role of NO cross talk from mTAL to surrounding VR in the renal medulla has been reviewed in detail elsewhere (19, 33) and will be discussed here largely with regard to its ROS-related counterregulatory functions. The present review will first summarize data showing that either the excess endogenous production or reduced scavenging of O 2 ·Ϫ or H 2 O 2 within the renal medulla results in a decrease in MBF and Na ϩ excretion, leading to hypertension and renal injury. Second, evidence will be summarized supporting the hypothesis that a high dietary salt intake results in increased luminal flow and delivery of NaCl to the mTAL, thereby signaling via both mechanical forces (stretch and shear) and increased Na ϩ transport, an increased mitochondrial and membrane NA-D(P)H oxidase production of O 2 ·Ϫ and H 2 O 2 . Third, studies will be reviewed showing that reduction of MBF leads to hypertension a...

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Nox2 redox signaling maintains essential cell populations in the brain

Cited by 247 publications

References 50 publications

Boronate probes for the detection of hydrogen peroxide release from human spermatozoa

Boronate probes for the detection of hydrogen peroxide release from human spermatozoa

Hyperpolarized ¹³ C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging

Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

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Nox2 redox signaling maintains essential cell populations in the brain

Cited by 247 publications

References 50 publications

Boronate probes for the detection of hydrogen peroxide release from human spermatozoa

Boronate probes for the detection of hydrogen peroxide release from human spermatozoa

Hyperpolarized 13 C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging

Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

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Hyperpolarized ¹³ C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging