Chunyan Hao

The role of neuropeptide Y and aquaporin 4 in the pathogenesis of intestinal dysfunction caused by traumatic brain injury

BACKGROUND Although the exact incidence is unknown, traumatic brain injury (TBI) can lead to intestinal dysfunction. It has important influence on the early nutrition and prognosis of TBI patients. Experiments were designed to study the roles of neuropeptide Y (NPY) and aquaporin 4 (AQP4) in the pathogenesis of intestinal dysfunction caused by TBI and to find some new solutions for the treatment of intestinal dysfunction after TBI. METHODS Forty adult male Wistar rats were randomly divided into control, mild trauma, moderate trauma, and severe trauma groups. TBI was induced by Feeneys impact method. Control animals were sham operated but not subjected to the impact test. All rats were killed 24 h after surgery. Blood samples were obtained from the abdominal aorta for enzyme-linked immunosorbent assay measurement of NPY concentrations. Jejunum segments 15 cm distal to the Treitz ligament were taken for analysis of NPY and AQP4 expression by polymerase chain reaction, Western blot, and immunohistochemistry. Pathologic changes in intestinal cell structure and ultrastructure were studied by light microscopy and transmission electron microscopy. RESULTS The specimens from different groups showed different degrees of structural changes, ranging from swelling and degeneration of villous epithelial cells to extensive denudation and collapse of the villi. The more severe the trauma, the more serious the degree of intestinal mucosal injury. Intestinal smooth muscle also showed varying degrees of edema and structural disorder. Electron microscopy showed that intestinal mitochondria had varying degrees of swelling and the structure of mitochondrial crista was disordered and even fractured. Plasma concentrations of NPY and jejunal gene and protein expressions of NPY and AQP4 increased significantly following TBI (P < 0.05), with greater increases at higher levels of injury. Moreover, there were positive correlations between NPY and AQP4 (P < 0.05). CONCLUSIONS Increasing grades of TBI caused increasing degrees of intestinal ischemia and edema, and thus caused increasingly severe intestinal dysfunction. AQP4 and NPY may be involved in the pathogenesis of intestinal dysfunction after TBI. Increased NPY levels may be responsible for intestinal ischemia and hypoxia, and AQP4 may play an important role in intestinal edema. Increased NPY levels may be one of the main causes for the increase in AQP4 after TBI.

Up-regulation of ANKDR49, a poor prognostic factor, regulates cell proliferation of gliomas

The Ankyrin repeat domain 49 (ANKRD49) is an evolutionarily conserved protein, which is related to mediate protein–protein interaction. However, the function of ANKRD49 in human glioma remains elusive. Mining through The Cancer Genome Atlas (TCGA) database, we found that the expression of ANKRD49 was increased in glioma tissues and that high expression of ANKRD49 was strongly associated with high disease grade and poor overall survival. To investigate the role of ANKRD49 in malignant glioma, lentivirus expressing shRNA targetting ANKRD49 was constructed in U251 and U87 malignant glioma cells. We demonstrated that ANKRD49 knockdown reduced the proliferation rate of U251 and U87 cells. Further mechanism analysis indicated that depletion of ANKRD49 led to the cell-cycle arrest and induced apoptosis in U251 and U87 cells. ANKRD49 knockdown also changed the expression of key effectors that are involved in stress response, cell cycle, and apoptosis, including p-HSP27 (heat shock protein 27), p-Smad2 (SMAD family member 2), p-p53, p-p38, p-MAPK (mitogen-activated protein kinase), p-SAPK/JNK (stress-activated protein kinase/c-jun n-terminal kinase), cleveagated Caspase-7, p-Chk1 (checkpoint kinase 1), and p-eIF2a (eukaryotic translation initiation factor 2a). Taken together, our findings implicate that ANKRD49 promotes the proliferation of human malignant glioma cells. ANKRD49 maybe an attractive target for malignant glioma therapy.

Knockdown of MRPL42 suppresses glioma cell proliferation by inducing cell cycle arrest and apoptosis

Mammalian mitochondrial ribosomal proteins are functionally involved in protein synthesis in mitochondrion. Recently numerous studies have illuminated the role of mitochondrion in cancer development. However, the precise function of mitochondrial ribosomal protein L42 (MRPL42) remains unclear. Here in the present study, we identified MRPL42 as a novel oncogene in glioma. By analyzing the Cancer Genome Atlas (TCGA) database, we first found that MRPL42 was significantly up-regulated in glioma tissues compared with normal tissues. Functionally, we silenced MRPL42 in glioma cells and revealed that MRPL42 knockdown largely blunted the proliferation of U251 and A172 cells. Mechanistically, our results suggested that MRPL42 silencing resulted in increased distribution of cell cycle in G1 and G2/M phases, while the S-phase decreased. In addition, the apoptosis and caspase3/7 activity were both activated after MRPL42 knockdown. Taken together, MRPL42 is a novel oncogene in glioma and might help us develop promising targetted therapies for glioma patients.