Human peptidylarginine deiminase type II: molecular cloning, gene organization, and expression in human skin

Ishigami, Akihito; Ohsawa, Tomonori; Asaga, Hiroaki; Akiyama, K.; Kuramoto, Masashi; Maruyama, Naoki

doi:10.1016/s0003-9861(02)00516-7

Cited by 98 publications

(65 citation statements)

References 31 publications

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“…However, citrullinated proteins comprise citrulline residues that result from post-translational modification of arginine; these include keratinization-related proteins (Ishigami et al 2002) and basic myelin protein, which makes up to 35% of the protein component of the central nervous system (Ishiyama et al 2001). It is a non-essential amino acid, synthesized almost exclusively in the mitochondrial matrix of enterocytes, catalyzed by pathways involving P5CS, carbamoyl phosphate synthase 1 (CPS1) and OTC (Fig.…”

Section: Discussionmentioning

confidence: 99%

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

et al. 2016

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Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not fulfil the stringent diagnostic criteria but have features resembling Leigh syndrome.We describe a unique presentation of Leigh-like syndrome in a 3-year-old boy with elevated 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening (NBS).Subsequent persistent plasma elevations of C5-OH and propionylcarnitine (C3) as well as fluctuating urinary markers were suggestive of multiple carboxylase deficiency (MCD). Normal enzymology and mutational analysis of genes encoding holocarboxylase synthetase (HLCS) and biotinidase (BTD) excluded MCD. Biotin uptake studies were normal excluding biotin transporter deficiency. His clinical features at 13 months of age comprised psychomotor delay, central hypotonia, myopathy, failure to thrive, hypocitrullinemia, recurrent episodes of decompensation with metabolic keto-lactic acidosis and an episode of hyperammonemia. Biotin treatment from 13 months of age was associated with increased patient activity, alertness,

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Section: Discussionmentioning

confidence: 99%

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

et al. 2016

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“…The subsequent procedures were performed as described above for PAD2 staining. For double-immunofluorescence staining, the sections were incubated in the following order: 10% normal donkey serum in PBS for 1 hour, rabbit polyclonal anti-PAD2 (1:100) 21 overnight at 4°C, lissamine rhodamine sulfonyl chloride (LRSC)-conjugated donkey anti-rabbit IgG (1: 200) (Jackson ImmunoResearch) for 1 hour at room temperature, washed, and blocked with 10% normal goat serum in PBS for 1 hour at room temperature and then incubated with various primary antibodies as follows: mouse monoclonal anti-GFAP antisera (1:400; DAKO, Copenhagen, Denmark), mouse monoclonal anti-NeuN (1:50) (Chemicon, Temecula, CA), mouse monoclonal anti-MBP (1:3000) overnight at 4°C and finally washed and incubated with fluorescein isothiocyanate-conjugated goat anti-mouse IgG (1:200) (Jackson ImmunoResearch). For microglia staining, the lectin Griffonia simplicifolia (GSA) was optimized by incubating the sections in 0.5 mg/ml of trypsin in 0.05 mol/L Tris-buffered saline containing 1 mmol/L CaCl 2 (pH 7.6) for 5 minutes at 37°C.…”

Section: Immunohistochemistry and Double-immunofluorescence Stainingmentioning

confidence: 99%

Accumulation of Citrullinated Proteins by Up-Regulated Peptidylarginine Deiminase 2 in Brains of Scrapie-Infected Mice

Jang

Kim

Choi

et al. 2008

The American Journal of Pathology

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Peptidylarginine deiminases (PADs), which are a group of posttranslational modification enzymes, are involved in protein citrullination (deimination) by the conversion of peptidylarginine to peptidylcitrulline in a calcium concentration-dependent manner. Among the PADs, PAD2 is widely distributed in various tissues and is the only type that is expressed in brain. To elucidate the involvement of protein citrullination by PAD2 in the pathogenesis of brain-specific prion diseases, we examined the profiles of citrullinated proteins using the brains of scrapie-infected mice as a prion disease model. We found that, compared with controls, increased levels of citrullinated proteins of various molecular weights were detected in different brain sections of scrapie-infected mice. In support of this data, expression levels of PAD2 protein as well as its enzyme activity were significantly increased in brain sections of scrapie-infected mice, including hippocampus, brain stem, and striatum. Additionally, the expression levels of PAD2 mRNA were increased during scrapie infection. Moreover, PAD2 immunoreactivity was increased in scrapie-infected brains, with staining detected primarily in reactive astrocytes. Using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry, various citrullinated proteins were identified in the brains of scrapie-infected mice, including glial fibrillary acidic protein, myelin basic protein, enolases, and aldolases. This study suggests that accumulated citrullinated proteins and abnormal activation of PAD2 may function in the pathogenesis of prion diseases and serve as potential therapeutic targets. Accumulation of misfolded proteins, posttranslational modification of proteins, alteration of free ion distribution, and perturbation of cellular redox homeostasis are general features of progressive neurodegenerative disorders. These changes have been observed consistently as part of the neuropathogenesis and neuropathology of prion diseases. Prion diseases are characterized by various neurological symptoms and common histopathological features such as spongiform degeneration of the central nervous system, reactive gliosis, neuronal loss, and, in some cases, formation of amyloid plaques. 1 It has been reported that all prion diseases are associated with the aberrant metabolism of prion protein (PrP). Conversion of the cellular prion protein (PrP C ) into an abnormal, protease-resistant and infectious isoform (PrP Sc ) is believed to be a principal molecular basis of prion diseases, 2 and the accumulation of PrP Sc in the central nervous system is thought to be responsible for neuronal loss and/or astrocytosis.

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“…Unlike the L-Arginine, L-Citrulline bypasses liver metabolism and is not considered as a substrate for Arginase [7,8]. L-Citrulline administration has a stimulating role in the L-Arginine production.…”

Section: Introductionmentioning

confidence: 99%

The Assessment of short-term effect of L-Citrulline on endothelial function via FMD to NMD ratio in known CAD patients: A randomized, cross-over clinical trial (Clinical trial number: NCT02638727)

Safi

Mahjoob

Nateghi

et al. 2017

Romanian Journal of Internal Medicine

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Background. Recent studies have confirmed the essential and paramount role of the L-Citrulline on the nitric oxide regulation and the endothelial function improvement.Materials and Methods. In this cross-over clinical trial, thirty patients, diagnosed with coronary artery disease (CAD) and flow mediated dilation to nitroglycerin dependent vasodilation (FMD/NMD) ratio less than 1, were included. The patients were randomly divided into two groups of 15 patients and underwent treatment by L-Citrulline or placebo for 15 days, in 2 step protocol. The indicators of assessment in the current study were the ratio of the FMD/NMD and FMD value.Results. In the current cross-over clinical trial, the mean of FMD to NMD ratio and mean FMD value of all patients before starting the protocol were 0.91 ± 0.08 and 4.04 ± 0.51 mm, respectively. The final results of study showed that following L-Citrulline administration, mean FMD to NMD ratio and mean FMD value were enhanced to: 1.03 ± 0.09 and 4.96 ± 0.72 mm, respectively, which were statistically significant (P<0.001 and P<0.001, respectively). However, following placebo administration, mean FMD to NMD ratio and mean FMD value were receded to: 0.92 ± 0.09 and 4.06 ± 0.22 mm, respectively, which were not statistically significant (P = 0.75 and P = 0.89, respectively). Moreover, the improvement of mean FMD to NMD ratio (0.12 ± 0.02) and mean FMD value (0.92 ± 0.16 mm), following L-Citrulline administration, were statistically significant in comparison with the change of mean FMD to NMD ratio (0.01 ± 0.002) and mean FMD value (0.02 ± 0.003), following placebo administration (P<0.001 and P<0.001, respectively).Conclusion. L-Citrulline treatment can lead to improvement of the endothelial function in patients diagnosed with CAD which are assessed via FMD to NMD ratio FMD value enhancements.

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Human peptidylarginine deiminase type II: molecular cloning, gene organization, and expression in human skin

Cited by 98 publications

References 31 publications

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

Accumulation of Citrullinated Proteins by Up-Regulated Peptidylarginine Deiminase 2 in Brains of Scrapie-Infected Mice

The Assessment of short-term effect of L-Citrulline on endothelial function via FMD to NMD ratio in known CAD patients: A randomized, cross-over clinical trial (Clinical trial number: NCT02638727)

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