Neuroprotection of taurine against bilirubin-induced elevation of apoptosis and intracellular free calcium ion in vivo.
Previous work has shown that taurine protected neurons against unconjugated bilirubin (UCB)-induced neurotoxicity by preventing cell apoptosis and maintaining intracellular Ca²⁺ homeostasis in primary neuron culture. This study investigates the neurotoxicity of hyperbilirubinemia and neuroprotection of taurine in a clinically relevant murine model in vivo. A hyperbilirubinemia baby mice model was established by intraperitoneal injection with UCB. After 24 h, the neural apoptotic level, transcriptional activity of caspase-3, and iCa²⁺ concentration were detected. It was found that UCB injection significantly increased both intracellular free Ca²⁺ concentrations and the activities of proapoptosis protease caspase-3, which is related to the elevation of neural apoptosis level. When baby mice were pretreated with 7.5 or 15 mg/kg body weight (bw) taurine for 4 h and then exposed to UCB, apoptotic death was significantly attenuated through down-regulation of activity of caspase-3 and i[Ca²⁺] in the brain. From these observations, it was concluded that taurine limits bilirubin-induced neural damage by inhibiting iCa²⁺ overload as well as decreasing activation of proapoptotic proteases caspase-3. This study might contribute to the development of taurine as a broad-spectrum agent for preventing and/or treating neural damage in neonatal jaundice.
Molecular Immunology, Center of Clinical laboratory, People's Hospital of Gansu Province, Gansu, P.R. China.
Xiaoling
X
Gao
Xi
X
Yang
Benzhong
B
Zhang
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001663:Bilirubin / Q000633:toxicity*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D004195:Disease Models, Animal; D005260:Female; D051556:Hyperbilirubinemia, Neonatal / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013654:Taurine / Q000494:pharmacology*
D061945:Caspase Inhibitors; D018696:Neuroprotective Agents; D013654:Taurine; D053148:Caspase 3; D001663:Bilirubin; D002118:Calcium