Changes in S-(2-succinyl)cysteine and advanced glycation end-products levels in mouse tissues associated with aging

Katsuta, Nana; Takahashi, Himeno; Nagai, Mime; Sugawa, Hikari; Nagai, Ryoji

doi:10.1007/s00726-022-03130-y

Cited by 8 publications

(15 citation statements)

References 38 publications

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“…(22) Isotope-labeled standards were obtained as previously described. (17) Pretreatment of the human serum was performed based on described previously. (17) Human serum (30 μl) and 5 μl of 10 μM [ 13 C 3 , 15 N 1 ] 2SC as internal standard were added to 660 μl of distilled water.…”

Section: Sample Collectionmentioning

confidence: 99%

“…(17) Pretreatment of the human serum was performed based on described previously. (17) Human serum (30 μl) and 5 μl of 10 μM [ 13 C 3 , 15 N 1 ] 2SC as internal standard were added to 660 μl of distilled water. It passed through Captiva ND Lipids cartridge (Agilent Technologies, Santa Clara, CA) containing 2.1 ml methanol and 0.1% (v/v) formic acid, and the eluted fraction was collected.…”

Section: Sample Collectionmentioning

confidence: 99%

“…(24,25) Isotope-labeled standards were obtained as previously described. (17) Pretreatment of the human serum was performed according to a previously described method. (26) Briefly, 70 μl of distilled water and 70 μl of human serum were mixed, it was filtered through a VIVASPIN 500 filter.…”

Section: Sample Collectionmentioning

confidence: 99%

“…Sample measurement was performed as described previously. (17) Briefly, quantification was performed by an internal standard method using standard curves constructed from mixtures of isotope and non-isotope labeling standards. LC separation was performed using an UltiMate 3000 HPLC system (Thermo Fisher Scientific, Waltham, MA).…”

Section: Measurement Of 2sc and Ages Levels By Lc-ms/msmentioning

confidence: 99%

“…(15) Succination occurs in various tissues; 2SC is detectable by an immunochemical method using a polyclonal anti-2SC antibody and an instrumental analysis, including gas chromatographymass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). (15)(16)(17) As metabolites in the blood are expected to reflect the metabolic abnormalities and pathologies, those analyses will play roles as not only biomarkers but also mechanism elucidation of the onset of diseases. However, few studies have investigated the changes in the level of 2SC with pathology due to its difficult analysis.…”

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confidence: 99%

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Mitochondrial stress and glycoxidation increase with decreased kidney function

Katsuta

Nagai

Saruwatari

et al. 2023

J. Clin. Biochem. Nutr.

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Mitochondrial stress increases the production of fumarate, an intermediate of the Krebs cycle. Fumarate non-enzymatically reacts with the thiol group of cysteine, leading to the production of S-(2-succinyl)cysteine. Here, we quantified the concentration of fumarate, the free form of S-(2-succinyl)cysteine, and advanced glycation end-products, including N ε -(carboxymethyl)lysine and N δ -(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine, in the serum of chronic kidney disease patients, using liquid chromatographytandem mass spectrometry and an enzymatic assay. In a crosssectional study, we evaluated the difference in metabolite concentration between healthy individuals (n = 22) and kidney transplant patients (n = 93). Additionally, we evaluated the metabolite concentration of end-stage renal disease patients (n = 17) before and 1, 3, 6, and 12 months after transplantation, in a longitudinal study. While the S-(2-succinyl)cysteine and AGEs levels were significantly increased in accordance with the rising chronic kidney disease severity, they were significantly decreased after transplantation. However, fumarate levels were only significantly different in end-stage renal disease patients. The S-(2-succinyl)cysteine levels correlated with the pre-existing kidney function marker. This study demonstrates that mitochondrial metabolic disorders contribute to impaired kidney function, and that measuring blood S-(2-succinyl)cysteine levels may be a minimally invasive way to evaluate the metabolic change in chronic kidney disease.

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