cyclin-d1 and Hyperammonemia

Hyperammonaemia is a serious metabolic disorder commonly observed in patients with hepatic failure. However, it is unknown whether hyperammonaemia has a direct adverse effect on the hepatocytes and thereby serves as both a cause and effect of hepatic failure.. The purposes were to determine whether hepatic injury can be caused by hyperammonaemia, and if so, screen the key genes involved in hyperammonaemia.. Hyperammonaemic rats were established via intragastric administration of the ammonium chloride solution. The liver tissues were assessed via biochemistry, histology, immunohistochemistry and microarray analysis. Selected genes were confirmed by quantitative RT-PCR.. Administration of the ammonium chloride caused the hyperammonaemia, accompanied with the changes of plasma markers indicating hepatic injury. A pathological assessment demonstrated increased apoptosis and higher level of cyclin D1 and cyclin A in hyperammonaemic rat liver. Microarray was performed on the liver samples and 198 differentially expressed genes were identified in hyperammonaemic rats and validated by quantitative RT-PCR. These genes were associated with many vital functional classes and belonged to different signal transduction pathways.. This study demonstrates that hyperammonaemia can directly induce hepatic injury via the hepatocyte apoptosis. Gene expression profile may provide the possible explanations and mechanisms for the hepatic injury induced by hyperammonaemia.

Topics: Ammonium Chloride; Animals; Apoptosis; Cyclin A; Cyclin D1; Disease Models, Animal; Gene Expression Profiling; Hyperammonemia; Liver; Male; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Rats, Sprague-Dawley

Two new human myeloma cell lines were established from pleural effusion and bone marrow malignant cells derived from a single patient, who manifested hyperammonemia associated with multiple myeloma, and these were characterized. Both lines possess t(11;14)(q13;q32) and t(8;14)(q24;q32) reciprocal translocations and overexpress cyclin D1, but not c-myc. Human myeloma lines including these new lines produced and secreted excess ammonia into culture medium more than non-myelomatous hematological cell lines. In addition, these two lines were revealed to have high surface CD7 expression correlated with relatively high mRNA expression by MP-RT-PCR. Among 8 human myeloma lines, half of them revealed significant surface expression of CD7 and a positive correlation between expression levels of protein and message. CD7 message was also detected in surface negative lines. Consequently, there may be posttranslational regulation of the CD7 molecule, whose cellular biological role in expressing cells has not been elucidated.

Topics: Adult; Ammonia; Antigens, CD7; Bone Marrow Cells; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 8; Cyclin D1; Humans; Hyperammonemia; Male; Multiple Myeloma; Pleural Effusion, Malignant; Proto-Oncogene Proteins c-myc; Translocation, Genetic; Tumor Cells, Cultured