Subject(s)
Hernia, Inguinal/surgery , Incidental Findings , Tomography, X-Ray Computed/methods , Urinary Bladder Diseases/surgery , Abdominal Pain/diagnosis , Abdominal Pain/etiology , Cholecystitis/diagnosis , Cholecystitis/drug therapy , Contrast Media , Hernia, Inguinal/diagnostic imaging , Herniorrhaphy/methods , Humans , Male , Middle Aged , Risk Assessment , Scrotum/diagnostic imaging , Scrotum/pathology , Urinary Bladder Diseases/diagnostic imagingABSTRACT
BACKGROUND: Peptidylarginine deiminases (PADs) are a group of posttranslational modification enzymes that citrullinate (deiminate) protein arginine residues, yielding citrulline residues. Citrullination of arginine residues abolishes their positive charge, markedly altering their structure. We undertook this study to investigate the actions of PADs in the kidney. METHODS: In male rats, we ligated the unilateral ureter, then analyzed the obstructed and contralateral kidneys 1 week later. Controls were rats simultaneously given sham operations. In another experiment, we ligated unilateral ureters of eight rats, four of which received a ureter-bladder anastomosis 1 week later. These rats were subjected to histologic examinations 5 weeks after unilateral ureteral obstruction (UUO). RESULTS: Reverse transcription-polymerase chain reaction (RT-PCR) revealed that, of PADs (type I, II, III, and IV), only PAD type II was expressed in kidneys. Western blot study showed that PAD type II expression and citrullinated protein content increased greatly in kidneys that underwent unilateral ureteral ligation compared to that in contralateral or sham-operated kidneys. Immunohistochemical analyses revealed that PAD type II was preferentially expressed by parietal epithelial cells and that only in Bowman's capsule were proteins citrullinated. Additionally, these PAD type II and citrullinated proteins in obstructed nephropathy were significantly attenuated by the release of the obstruction. Proteome analysis revealed that one of citrullinated proteins in the kidney should be actin. CONCLUSION: This result indicates that PAD type II and citrullinated proteins are suitable markers of Bowman's capsule. Not only are these markers preferentially expressed in Bowman's capsules but their expression is also increased in damaged kidneys by UUO, features that promise the further clarification of kidney diseases.
Subject(s)
Citrulline/metabolism , Kidney Glomerulus/metabolism , Kidney Glomerulus/physiopathology , Ureteral Obstruction/metabolism , Ureteral Obstruction/physiopathology , Actin Cytoskeleton/metabolism , Animals , Biomarkers , Blood Urea Nitrogen , Creatinine/blood , Epithelial Cells/enzymology , Hydrolases/genetics , Male , Peptide Mapping , Protein-Arginine Deiminase Type 2 , RNA, Messenger/analysis , Rats , Rats, Sprague-DawleyABSTRACT
A 37-year-old Japanese woman was referred from another clinic to confirm the diagnosis of myotonia congenita. She had experienced cold-induced myotonia and muscle stiffness from early childhood. Of her three children, her elder son and her daughter have clinical features similar to hers. They experience neither grip nor percussion myotonia during warm weather, whereas myotonia is provoked by cold. Her younger son has no symptoms. DNA analyses of the SCN4A gene showed a C to T transition at nucleotide position 3938 in exon 22 of SCN4A (Thr1313Met) in all three affected family members, but not in the unaffected son. Paramyotonia congenita, the prevalence of which is very low in Japan, was diagnosed based on their clinical features and DNA analysis results.
