The regulation mechanism of protein kinase Cδ on arsenic liver injury caused by coal-burning

Abstract

To investigate the effects of mRNA transcriptional and protein expressions of protein kinase Cδ (PKCδ) on the development of arsenic liver injury caused by coal-burning. Population study:133 arsenic exposures were selected as arsenic exposure groups including the ward non-patient group (25 cases) , no obvious hepatopathy group (38 cases) , mild (43 cases) and moderate to severe hepatopathy group (27 cases) from the area with endemic arsenism in Guizhou province. Another 34 healthy residents were selected as the control group in non-arsenic pollution village. The urine and peripheral blood were collected from the subjects. The arsenic contents in urine and mRNA expressions of PKCδ in peripheral blood were detected. Animal experiment study:thirty wistar rats were randomly by random number table divided into control group, drinking water arsenic poisoning group and coal-burning arsenic poisoning group (i.e., low, medium and high arsenic contaminated grain group) by random number table method, including 6 rats in each group. The control group was fed normally for 3 months, drinking water arsenic poisoning group and coal-burning arsenic poisoning groups were fed respectively with 10 mg/kg As2O3 solution and different concentrations (25, 50 and 100 mg/kg) of arsenic-containing feed which was persisted 3 months. The arsenic contents in urine, mRNA expression levels of PKCδ in peripheral blood and liver tissue and the protein expression levels of phosphorylated protein kinase Cδ(pPKCδ) in liver tissue were detected. The median(quartile) of arsenic contents in urine were 25.58 (18.62-40.73), 56.66 (38.93-76.77), 64.90 (39.55- 98.37) and 75.47 (41.30-109.70) µg/g Cr respectively for the non-patient group, no obvious hepatopathy group, mild and moderate to severe hepatopathy group. The levels were higher than that in the control group (23.34 (17.84-37.45) µg/g Cr) (P < 0.05), except for the ward non-patient group. The arsenic contents in rat urine were 2223.61 (472.98-3976.73), 701.16 (194.01-1300.27), 1060.94 (246.33-2585.47) and 3101.11 (1919.97-5407.07) µg/g Cr, respectively for the drinking water arsenic poisoning group, the low, medium and high dosage arsenic grain contamination groups, all higher than that in the control group (94.32 (22.65-195.25) µg/g Cr) (P < 0.05) . The protein expressions of pPKCδ in liver tissue were 324.83 ± 25.06, 278.50 ± 30.57, 308.83 ± 34.67 and 326.33 ± 35.09, which were significantly higher than that in the control group (240.17 ± 28.07) (P < 0.05) . The protein expression levels of pPKCδ in liver cell membrane were 0.49 ± 0.06,0.33 ± 0.05,0.37 ± 0.06 and 0.50 ± 0.08, which were significantly higher than that in the control group (0.28 ± 0.04) (P < 0.05) . The protein expression levels of pPKCδ in liver cell cytoplasm were 0.38 ± 0.06,0.31 ± 0.05, 0.35 ± 0.05 and 0.36 ± 0.05, which were significantly higher than that in the control group (0.24 ± 0.05) (P < 0.05). The arsenic may regulate protein expressions of pPKCδ and induce its membrane translocation, and cause the development of arsenic liver injury caused by coal-burning.