Gap junctions mediate direct communication between cells; however, toxicological cascade triggered by nonessential metals can abrogate cellular signaling mediated by gap junctions. Although cadmium (Cd) is known to induce apoptosis in organs and tissues, the mechanisms that underlie gap junction activity in Cd-induced apoptosis in BRL 3A rat liver cells has yet to be established. In this study, we showed that Cd treatment decreased the cell index (a measure of cellular electrical impedance) in BRL 3A cells. Mechanistically, we found that Cd exposure decreased expression of connexin 43 (Cx43), increased expression of p-Cx43 and elevated intracellular free Ca2+ concentration, corresponding to a decrease in gap junctional intercellular communication. Gap junction blockage pretreatment with 18β-glycyrrhizic acid (GA) promoted Cd-induced apoptosis, involving changes in expression of Bax, Bcl-2, caspase-3 and the mitochondrial transmembrane electrical potential (Δψm). Additionally, GA was found to enhance ERK and p38 activation during Cd-induced activation of mitogen-activated protein kinases, but had no significant effect on JNK activation. Our results indicated the apoptosis-related proteins and the ERK and p38 signaling pathways may participate in gap junction blockage promoting Cd-induced apoptosis in BRL 3A cells.
Animals ; Apoptosis/*drug effects ; Cadmium/*toxicity ; Calcium/metabolism ; Cell Communication/drug effects ; Connexin 43/genetics ; Enzyme Activation/drug effects ; Gap Junctions/*drug effects ; Gene Expression Regulation/drug effects ; Hepatocytes/cytology/*drug effects ; Rats ; Signal Transduction/drug effects

Objective: To explore the value of bioelectrical impedance analysis in evaluating hemodialysis patients′ nutritional status. Methods: Cross-sectional design was employed to evaluate 193 hemodialysis patients′ nutritional status in a Level 3 hospital in Zhuhai, with bioelectrical impedance analysis, modified quantitative subjective global assessment, physical and biochemical measurement. The correlation between each index and the predictive effect of bioelectrical impedance analysis on malnutrition of patients were analyzed. Results: According to bioelectrical impedance analysis, hemodialysis patients′ average muscle mass was (44.06±8.84) kg, body fat rate was (19.81±8.89)%, fat free mass index was (17.70±2.45) kg/m², presumed bone mass was (2.49±0.46) kg, and extracellular water rate was (40.54±3.75)%. The bioelectrical impedance analysis indexes were significantly correlated with most other nutritional evaluation indexes (P<0.05). The muscle mass and bone mass of the malnourished group were lower than that of the well-nourished group (P<0.01). Multivariable logistic regression analysis found that body fat rate (OR=0.94, 95%CI 0.89-0.99), fat free body mass index (OR=0.79, 95%CI 0.66-0.93) were associated with lower risk of malnutrition, age (OR=1.08, 95% CI 1.04-1.12), dialysis age (OR=1.02, 95%CI 1.01-1.04), high sensitive C reactive protein (OR=1.11, 95%CI 1.03-1.23) were associated with higher risk of malnutrition. Conclusion Bioelectrical impedance analysis is a valid measurement on evaluating maintenance hemodialysis patients′ nutritional status. There has a high prevalence of malnutrition in hemodialysis patients. The lower risk of malnutrition is associated with higher body fat rate and higher fat free mass index, and the higher risk of malnutrition is associated with older age, longer dialysis age and higher level of high sensitive C reactive protein.