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Kalita, J.; Kumar, V.; Misra, U.K.
Molecular neurobiology, 12/2016, Volume: 53, Issue: 10Journal Article
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.
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