AIMTo observe the protective role of pituitary adenylate cyclase activating polypeptide (PACAP) on hippocampal neuronal apoptosis induced by beta amyloid peptide in the culture.

METHODSHippocampal neurons were isolated from 1d old SD rat and neuronal survival and apoptosis were measured by MTT assay and DNA ladder.

RESULTS25 micromol/L Abeta could induce neuron apoptosis while co-treatment with PACAP could increase the survival of hippocampal neurons. The antagonist of PACAP receptor, P6-27, could reverse the effect of PACAP.

CONCLUSIONPACAP could protects cultured neurons from the neurotoxicity of Abeta through the activation of PACAP receptor and may have a bright use in treatment of neurodegenerative disease.

Amyloid beta-Peptides ; toxicity ; Animals ; Apoptosis ; drug effects ; Cells, Cultured ; Hippocampus ; cytology ; Neurons ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide ; metabolism

AIMTo observe the relationship between amyloid beta-protein (Abeta) and oxidative stress and the protective role of pituitary adenylate cyclase activating polypeptide (PACAP, PACAP-27) against damage induced by oxidative stress (H2O2) in neurem-2a cells.

METHODSWith cultured neuro-2a cells the cell survival and apoptosis were measured by MTT assay, Hoechest33258 staining, DNA ladder and the percentage of small DNA fragment.

RESULTSConcentration-dependent toxicity was induced with H2O2 treatment for 24 h. The neurotoxicity of H2O2 was increased by about 10 times with cotreatment neurons with amyloid beta-protein fragment 25-35 (Abeta(25-35)). While decrease the percentage of small DNA fragmentation the cell survival was increased with co-treatment with PACAP-27(which were added to the culture everyday). The effect of PACAP was not reversed with antagonist of PACAP receptor, PACAP(6-27).

CONCLUSIONAbeta and H2O2 can promote each other's neurotoxicity. Cultured neurons were protected by PACAP27 from the neurotoxicity of H2O2 but not through the activation of PACAP-27 receptor.

Amyloid beta-Peptides ; toxicity ; Apoptosis ; Cell Survival ; Cells, Cultured ; Humans ; Hydrogen Peroxide ; pharmacology ; Neurons ; cytology ; drug effects ; Oxidative Stress ; Pituitary Adenylate Cyclase-Activating Polypeptide ; pharmacology

MTT analysis and intracellular calcium measurement by using confocal laser scanning microscopy were used to study the possible mechanism of protective effect of pituitary adenylate cyclase activating polypeptide 27 (PACAP27) from beta amyloid protein (Abeta)-induced neurotoxicity. The results showed that treatment with PACAP (less than 0.1 micromol/L) increased the survival and reproductive ability of neuro-2a cells and protected the neuro-2a cells from being injured by Abeta. The protective effect of PACAP27 was reversed by the competitive PACAP receptor antagonist PACAP6-27. An increase in intracellular calcium was observed when the cells were challenged with Abeta and PACAP. But the calcium increase induced by Abeta kept stable for a long time while PACAP caused a transient rise in intracellular calcium. The intracellular calcium increase induced by Abeta was blocked by pretreatment with PACAP for 10 min. It is suggested that the neuroprotective effect of PACAP against neuronal damage induced by Abeta may result from its role in inhibiting the sustained rise in intracellular calcium.
Amyloid beta-Peptides ; antagonists & inhibitors ; toxicity ; Calcium ; metabolism ; Calcium Channels ; metabolism ; Cell Line, Tumor ; Humans ; Neuroblastoma ; pathology ; Neuroprotective Agents ; pharmacology ; Pituitary Adenylate Cyclase-Activating Polypeptide ; pharmacology

OBJECTIVE: To study the value of serum gamma-glutamyl transpeptidase (GGT) combined with direct bilirubin (DB) in the diagnosis of biliary atresia. METHODS: A total of 667 infants with cholestasis who were hospitalized and treated from July 2010 to December 2018 were enrolled as subjects. According to the results of intraoperative cholangiography and follow-up, they were divided into biliary atresia group with 234 infants and cholestasis group with 433 infants. The two groups were compared in terms of age of onset, sex, and serum levels of total bilirubin (TB), DB, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), and GGT. A receiver operating characteristic (ROC) curve analysis was performed for indices with statistical significance, and the area under the ROC curve (AUC) and the optimal cut-off value for diagnosis were calculated. RESULTS: The biliary atresia group had a significantly younger age of onset than the cholestasis group (P<0.001). There were no significant differences in sex, ALT, and AST between the two groups (P>0.05), while the biliary atresia group had significantly higher serum levels of TB, DB, TBA, and GGT than the cholestasis group (P<0.05). GGT combined with DB had the highest AUC of 0.892 (95% confidence interval: 0.868-0.916) in the diagnosis of biliary atresia. At the optimal cut-off values of 324.0 U/L for GGT and 115.1 μmmol/L for DB, GGT combined with DB had a sensitivity of 79.8% and a specificity of 83.2% in the diagnosis of biliary atresia. CONCLUSIONS GGT combined with DB has high sensitivity and specificity in the diagnosis of biliary atresia and can be used as an effective indicator for diagnosis of biliary atresia in infants.
Alanine Transaminase ; Aspartate Aminotransferases ; Biliary Atresia ; diagnosis ; Bilirubin ; Humans ; Infant ; gamma-Glutamyltransferase ; blood