Cystathionine β-synthase is enriched in the brains of Down’s patients

Ichinohe, Akiko; Kanaumi, Takeshi; Takashima, Sachio; Enokido, Yasushi; Nagai, Yasuo; Kimura, Hideo

doi:10.1016/j.bbrc.2005.10.118

Cited by 118 publications

(85 citation statements)

References 15 publications

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“…However, the concentrations of sulfide measured in these studies, which contained H 2 S released from acid-labile sulfur in addition to free H 2 S, were overestimated (23). Recently, the basal concentrations of H 2 S in tissues have been measured and found to be much lower than those previously reported (18,24,36).…”

Section: Introductionmentioning

confidence: 57%

“…In the brain, astrocytes express CBS, which is intensively localized to cerebellar molecular layer and hippocampal dentate gyrus (16,23) (Fig. 3).…”

Section: Production Of H 2 Smentioning

confidence: 99%

“…Because of trisomy 21 in Down syndrome (DS), CBS levels in patients are predicted to be 1.5-fold greater than those in normal individuals. However, the expression of CBS mRNA is 12 times greater in myeloblasts of DS children than in those of normal individuals, and the levels of CBS in DS patients are 2.4-2.9 times greater than those in age-matched normal individuals (23,64). Individuals with DS almost invariably develop an Alzheimer type of dementia (AD).…”

mentioning

confidence: 98%

“…CBS is localized to astrocytes and the surrounding senile plaques in the brains of DS patients with AD. The overexpression of CBS may cause a developmental abnormality in cognition in DS children and that may lead to AD in DS adults (23). Overproduction of H 2 S may cause the mental disturbance in DS.…”

mentioning

confidence: 99%

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Hydrogen Sulfide Is a Signaling Molecule and a Cytoprotectant

Kimura

Shibuya²,

Kimura³

2012

Antioxidants & Redox Signaling

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256

190

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Significance: Accumulating evidence shows that hydrogen sulfide may function as a signaling molecule in processes such as neuromodulation in the brain and smooth muscle relaxation in the vascular system. It also has a cytoprotective effect, since it can protect neurons and cardiac muscle from oxidative stress and ischemiareperfusion injury, respectively. Hydrogen sulfide can also modulate inflammation, insulin release, and angiogenesis. Recent Advances: The regulation of the activity of 3-mercaptopyruvate sulfur transferase (3MST) along with cysteine aminotransferase (CAT), one of the H 2 S producing pathways, has been demonstrated. The production of H 2 S by the pathway, which is regulated by Ca 2+ and facilitated by thioredoxin and dihydrolipoic acid, is also involved in H 2 S signaling as well as cytoprotection. Sulfur hydration of proteins by H 2 S has been proposed to modulate protein functions. H 2 S-sensitive fluorescent probes, which enable us to measure the localization of H 2 S in real time, have been developed. Critical Issues: The basal concentrations of H 2 S have recently been measured and found to be much lower than those initially reported. However, the concentration of H 2 S reached in stimulated cells, as well as the regulation of H 2 S producing enzymes is not well understood. It has been proposed that some of the effects of H 2 S on the regulation of enzymes and receptors might be explained through the properties of sulfane sulfur (S 0 ), another form of active sulfur. Future Directions: The determination of H 2 S concentrations in activated cells using new methods including H 2 S-sensitive fluorescent probes, as well as the investigation of the effects of H 2 S using specific inhibitors, may provide better understanding of the physiological function of this molecule. Clarifying mechanisms of H 2 S activity may also facilitate the development of new therapeutic compounds. Antioxid. Redox Signal. 17, 45-57.

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Section: Introductionmentioning

confidence: 57%

“…In the brain, astrocytes express CBS, which is intensively localized to cerebellar molecular layer and hippocampal dentate gyrus (16,23) (Fig. 3).…”

Section: Production Of H 2 Smentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

See 2 more Smart Citations

Hydrogen Sulfide Is a Signaling Molecule and a Cytoprotectant

Kimura

Shibuya²,

Kimura³

2012

Antioxidants & Redox Signaling

Self Cite

256

190

View full text Add to dashboard Cite

show abstract

“…In contrast, the enhanced flux of Met to the trans-sulfuration pathway that associates with increased Cth expression may contribute to the longevity found in Ames dwarf mice (61). CBS is expressed highly in both human and mouse brains (15,62), and CTH activity is 100-fold higher in the human brain than mouse brain (63). Mental retardation is commonly observed in CBS-deficient patients (10), and Cbs Ϫ/Ϫ mice displayed impaired learning in the passive avoidance test (16).…”

Section: Cbsmentioning

confidence: 99%

Cystathionine γ-Lyase-deficient Mice Require Dietary Cysteine to Protect against Acute Lethal Myopathy and Oxidative Injury

Ishii

Akahoshi

Yamada

et al. 2010

Journal of Biological Chemistry

206

229

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Cysteine is considered a nonessential amino acid in mammals as it is synthesized from methionine via trans-sulfuration. However, premature infants or patients with hepatic failure may require dietary cysteine due to a lack of cystathionine ␥-lyase (CTH), a key trans-sulfuration enzyme. Here, we generated CTH-deficient (Cth ؊/؊ ) mice as an animal model of cystathioninemia/cystathioninuria. Cth ؊/؊ mice developed normally in general but displayed hypercystathioninemia/hyperhomocysteinemia though not hypermethioninemia. When fed a low cyst(e)ine diet, Cth ؊/؊ mice showed acute skeletal muscle atrophy (myopathy) accompanied by enhanced gene expression of asparagine synthetase and reduced contents of glutathione in livers and skeletal muscles, and intracellular accumulation of LC3 and p62 in skeletal myofibers; they finally died of severe paralysis of the extremities. Cth ؊/؊ hepatocytes required cystine in a culture medium and showed greater sensitivity to oxidative stress. Cth ؊/؊ mice exhibited systemic vulnerability to oxidative injury, which became more prominent when they were fed the low cyst(e)ine diet. These results reveal novel roles of trans-sulfuration previously unrecognized in mice lacking another trans-sulfuration enzyme cystathionine ␤-synthase (Cbs ؊/؊ ). Because Cbs ؊/؊ mice display hyperhomocysteinemia and hypermethioninemia, our results raise questions against the homocysteine-based etiology of CBS deficiency and the current newborn screening for homocysteinemia using Guthrie's method, which detects hypermethioninemia.

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Oxidation of Hydrogen Sulfide to Polysulfide and Thiosulfate by a Carbon Nanozyme: Therapeutic Implications with an Emphasis on Down Syndrome

et al. 2023

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Hydrogen sulfide (H2S) is a noxious, potentially poisonous, but necessary gas produced from sulfur metabolism in humans. In Down Syndrome (DS), the production of H2S is elevated and associated with degraded mitochondrial function. Therefore, removing H2S from the body as a stable oxide could be an approach to reducing the deleterious effects of H2S in DS. In this report we describe the catalytic oxidation of hydrogen sulfide (H2S) to polysulfides (HS2+n−) and thiosulfate (S2O32−) by poly(ethylene glycol) hydrophilic carbon clusters (PEG‐HCCs) and poly(ethylene glycol) oxidized activated charcoal (PEG‐OACs), examples of oxidized carbon nanozymes (OCNs). We show that OCNs oxidize H2S to polysulfides and S2O32− in a dose‐dependent manner. The reaction is dependent on O2 and the presence of quinone groups on the OCNs. In DS donor lymphocytes we found that OCNs increased polysulfide production, proliferation, and afforded protection against additional toxic levels of H2S compared to untreated DS lymphocytes. Finally, in Dp16 and Ts65DN murine models of DS, we found that OCNs restored osteoclast differentiation. This new action suggests potential facile translation into the clinic for conditions involving excess H2S exemplified by DS.

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Cystathionine β-synthase is enriched in the brains of Down’s patients

Cited by 118 publications

References 15 publications

Hydrogen Sulfide Is a Signaling Molecule and a Cytoprotectant

Hydrogen Sulfide Is a Signaling Molecule and a Cytoprotectant

Cystathionine γ-Lyase-deficient Mice Require Dietary Cysteine to Protect against Acute Lethal Myopathy and Oxidative Injury

Oxidation of Hydrogen Sulfide to Polysulfide and Thiosulfate by a Carbon Nanozyme: Therapeutic Implications with an Emphasis on Down Syndrome

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