RESUMO
Glycerophospholipids, which are components of biomembranes, are formed de novo by the Kennedy pathway and subsequently mature through the Lands cycle. Lysophospholipid acyltransferases (LPLATs) are key enzymes in both pathways and influence the fatty acid composition of biomembranes. Neuronal differentiation is characterized by neurite outgrowth, which requires biomembrane biosynthesis. However, the role of LPLATs in neuronal differentiation remains unknown. In this study, we examined whether LPLATs are involved in neuronal differentiation using all-trans-retinoic acid (ATRA)-treated P19C6 cells. In these cells, mRNA levels of lysophosphatidylethanolamine acyltransferase (LPEAT)-1/membrane-bound O-acyltransferase (MBOAT)-1 were higher than those in undifferentiated cells. LPEAT enzymatic activity increased with 16:0- and 18:1-CoA as acyl donors. When LPEAT1/MBOAT1 was knocked down with small interfering RNA (siRNA), outgrowth of neurites and expression of neuronal markers decreased in ATRA-treated P19C6 cells. Voltage-dependent calcium channel activity was also suppressed in these cells transfected with LPEAT1/MBOAT1 siRNA. These results suggest that LPEAT1/MBOAT1 plays an important role in neurite outgrowth and function.-Tabe, S., Hikiji, H., Ariyoshi, W., Hashidate-Yoshida, T., Shindou, H., Okinaga, T., Shimizu, T., Tominaga, K., Nishihara, T. Lysophosphatidylethanolamine acyltransferase 1/membrane-bound O-acyltransferase 1 regulates morphology and function of P19C6 cell-derived neurons.
Assuntos
Aciltransferases/metabolismo , Regulação Enzimológica da Expressão Gênica/fisiologia , Neurônios/citologia , Aciltransferases/genética , Animais , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Tretinoína/farmacologiaRESUMO
Glycerophospholipids, a primary component of cellular membranes, play important structural and functional roles in cells. In the remodelling pathway (Lands' cycle), the concerted actions of phospholipase As and lysophospholipid acyltransferases (LPLATs) contribute to the incorporation of diverse fatty acids in glycerophospholipids in an asymmetric manner, which differ between cell types. In this study, the role of LPLATs in osteoblastic differentiation of C2C12 cells was investigated. Gene and protein expression levels of lysophosphatidylcholine acyltransferase 2 (LPCAT2), one of the LPLATs, increased during osteoblastic differentiation in C2C12 cells. LPCAT2 knockdown in C2C12 cells downregulated the expression of osteoblastic differentiation markers and the number and size of lipid droplets (LDs) and suppressed the phosphorylation of Smad1/5/9. In addition, LPCAT2 knockdown inhibited Snail1 and the downstream target of Runx2 and vitamin D receptor (VDR). These results suggest that LPCAT2 modulates osteoblastic differentiation in C2C12 cells through the bone morphogenetic protein (BMP)/Smad signalling pathway.
RESUMO
OBJECTIVES: We evaluated the relationships between depth of invasion (DOI) of tongue cancer, as measured with preoperative T1- and T2-weighted magnetic resonance imaging (MRI) and postoperative histopathologic (Path) specimens, with cervical lymph node metastasis (CLNM) and tumor stage. We also calculated the correlation of MRI and Path DOI measurements. STUDY DESIGN: This retrospective study included 101 patients who had squamous cell carcinoma of the tongue and were treated surgically. Two observers measured DOI on all 3 modalities. RESULTS: DOI thresholds for predicting CLNM with high diagnostic efficacy were 6.99 mm and 8.32 mm for MRI and 5 mm for Path. DOI values from all modalities were significantly different for tumors with and without CLNM (P < .01) and for the 4 TNM stages (P ≤ .05), with increasing values corresponding to advancement in tumor stage. Addition of DOI changed the T level of many tumors based on the new TNM (tumor-node-metastasis) classification. The correlation coefficient between DOI calculated on each MRI sequence and Path was 0.90. CONCLUSIONS: MRI-derived DOI accurately reflected the subsequent metastatic status and degree of progression of tumor stages, with a strong positive correlation to Path values, and may be considered a predictor of tumor stage and CLNM.
Assuntos
Neoplasias da Língua , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Imageamento por Ressonância Magnética , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias da Língua/diagnóstico por imagem , Neoplasias da Língua/patologiaRESUMO
OBJECTIVES: The shapes of gubernaculum tracts (GTs) in molars as accessional teeth remain unidentified. To elucidate imaging peculiarities of GTs in molars with aging on multidetector-row computed tomography (MDCT). MATERIAL AND METHODS: This retrospective study was conducted using CT images, including maxillary and mandibular molars, with no abnormal findings from 239 patients. Shapes of alveolar bone, GTs, and dental sacs of the maxillary and mandibular molars were analyzed multi-sectionally. Correlations between 2- and 3-dimensional imaging figures of GTs in molars and chronological age or stage of molar formation were analyzed. RESULTS: Some forms of GTs in maxillary and mandibular third molars were observed. In the early stage, GTs were visualized as bone defect lines on the dentition and grooves on the mesial alveolar crest continuous with the dental sac to mesial tooth bud. GTs of the third molar formed a J-shape in maxillary teeth and Y-shape in mandibular teeth in the middle stage, as alveolar bone around the GT developed. In the mature stage, the course of the GT changed to straight and perpendicular. Some GT forms were also identified in first and second molars. Significant correlations were found between GT alterations and chronological age or stage of molar formation. Moreover, tracts continuing from the distal side of mandibular third molars were detected. CONCLUSIONS: This paper describes the peculiarities and process of progression for GTs in molars, and the existence of tracts continuing from the distal side of mandibular third molars, unlikely dentition with deciduous predecessors. These preliminary data should prove beneficial for studies focusing on GTs in molars.
Assuntos
Gubernáculo , Dente Molar , Humanos , Dente Molar/diagnóstico por imagem , Dente Serotino/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Glycerophospholipids have important structural and functional roles in cells and are the main components of cellular membranes. Glycerophospholipids are formed via the de novo pathway (Kennedy pathway) and are subsequently matured in the remodeling pathway (Lands' cycle). Lands' cycle consists of two steps: deacylation of phospholipids by phospholipases A2 and reacylation of lysophospholipids by lysophospholipid acyltransferases (LPLATs). LPLATs play key roles in the maturation and maintenance of the fatty acid composition of biomembranes, and cell differentiation. We examined whether LPLATs are involved in chondrogenic differentiation of ATDC5 cells, which can differentiate into chondrocytes. Lysophosphatidylcholine acyltransferase 4 (LPCAT4) mRNA expression and LPCAT enzymatic activity towards 18:1-, 18:2-, 20:4-, and 22:6-CoA increased in the late stage of chondrogenic differentiation, when mineralization occurred. LPCAT4 knockdown decreased mRNA and protein levels of chondrogenic markers as well as Alcian blue staining intensity and alkaline phosphatase activity in ATDC5 cells. These results suggest that LPCAT4 plays important roles during the transition of chondrocytes into hypertrophic chondrocytes and/or a mineralized phenotype.