title: A Study on Apoptosis and Anti-apoptotic Status in Wilson Disease.
abstract: Wilson disease (WD) is characterized by hepatolenticular degeneration, but there is no report on apoptosis and anti-apoptotic markers in WD patients with neurological manifestation (WDN). The aim of this study was to evaluate active caspase-3 and X-linked inhibitors of apoptosis protein (XIAP) level in WDN and correlate these with disease severity and markers of death (tumor necrosis factor-alpha (TNF-α), interleukin (IL)-8, malondialdehyde (MDA), and Cu) and survival signals (glutathione). Fifty-four patients with WDN and 36 healthy matched controls were included. Their severity, Burke-Fahn-Marsden (BFM) scores, blood counts, hemoglobin, serum chemistry, ceruloplasmin, and free copper and 24-h urinary copper were measured. Cranial MRI findings were noted. Serum active caspase-3, XIAP, TNF-α, IL-8, and plasma glutathione and MDA were measured using enzyme-linked immunosorbent assay (ELISA), flow cytometry, and spectrophotometer respectively. In the patients with WDN, active caspase-3 (0.55 ± 0.11 vs 0.38 ± 0.06 ng/ml), TNF-α (76.05 ± 29.01 vs 36.05 ± 21.01 pg/ml), IL-8 (590.19 ± 89.19 vs 193.43 ± 71.01 pg/ml), and MDA (4.92 ± 0.39 vs 3.43 ± 0.21 nmol/ml) levels were increased whereas XIAP (84.66 ± 10.39 vs 95.76 ± 10.11 ng/ml) and glutathione (GSH) (2.03 ± 0.29 vs 2.98 ± 0.27 mg/dl) levels were decreased compared to controls. Active caspase-3 was correlated with neurological severity (r = 0.48), BFM score (r = 0.37), ceruloplasmin (r = -0.39), hemoglobin (r = -0.34), and serum Cu (r = 0.39). XIAP levels were correlated with neurological severity (r = -0.40), BFM (r = -0.51), serum Cu (r = -0.42), and ceruloplasmin (r = 0.34). The XIAP level positively correlated with survival (GSH) and inversely with death signals (TNF-α, IL-8, MDA and free serum Cu) whereas active caspase-3 positively correlated with death (TNF-α, IL-8, serum Cu, MDA) and inversely with survival signal (GSH). Serum active caspase-3 level increased in WDN and positively correlated with the severity of disease, death signals (TNF, IL-8, MDA, and free Cu) and inversely with GSH and XIAP.
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow, 226014, India. jayanteek@yahoo.com.
authors.forename: J
authors.initials: J
authors.lastname: Kalita
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow, 226014, India.
authors.forename: V
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow, 226014, India.
authors.forename: U K
authors.initials: UK
authors.lastname: Misra
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D002648:Child; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006527:Hepatolenticular Degeneration / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D012044:Regression Analysis; D012886:Skull / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism; D055815:Young Adult
chemical_list: D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D008315:Malondialdehyde; D053148:Caspase 3; D005978:Glutathione
keywords: Apoptosis; Caspase; Copper; Cytokine; Glutathione; Malondialdehyde; Wilson disease; XIAP