ABSTRACT
Plasma cholesterol is increased in normal aging in both rodents and humans. This is associated with reduced elimination of cholesterol and decreased receptor-mediated clearance of plasma low-density lipoprotein (LDL) cholesterol. The aims of this study were: (1) to determine age-related changes in plasma lipid profiles, and (2) to determine the effect of fenofibrate, an activator of peroxisome proliferator activated receptor alpha (PPAR alpha), on plasma lipid profiles in normal rats on a standard diet. Male Sprague-Dawley (SD) rats (n=15) were fed standard chow and water from 10 to 25 weeks of age. During that period, we measured daily food intake, body weight, fasting and random blood glucose levels, plasma total cholesterol (TC), triglycerides (TG), and free fatty acid (FFA) levels. At 20 weeks of age, all rats were randomly divided into two groups: a fenofibrate group (in which rats were gavaged with 300 mg/kg/day of fenofibrate) and a control group (gavaged with water). Fenofibrate treatment lasted 5 weeks. There were no significant changes in daily food intake, blood glucose, and plasma TG level with age. Body weight, plasma TC, and FFA levels were significantly increased with age. Fenofibrate significantly decreased plasma concentrations of TC and FFA, which had been increased with age. However, fenofibrate did not influence the plasma concentration of TG, which had not increased with age. These results suggest that fenofibrate might have a novel role in preventing age-related hypercholesterolemia in SD rats on a normal diet.
Subject(s)
Animals , Humans , Male , Rats , Aging , Blood Glucose , Body Weight , Cholesterol , Diet , Eating , Fasting , Fenofibrate , Hypercholesterolemia , Lipoproteins , Plasma , PPAR alpha , Rats, Sprague-Dawley , Rodentia , Triglycerides , WaterABSTRACT
Homer protein was identified based on its rapid induction in rat hippocampal granule cell neurons following excitatory synaptic activity. Although the presence of the Homer gene in the peripheral tissues has been observed in previous reports, the physiological function of the Homer protein in these tissues has not been noted. In this experiment, a Homer-2a cDNA fragment was successfully amplified by RTPCR in the involuting phase of human hemangioma but not in the human vascular malformation and normal vessel. After isolation of full Homer cDNA in a mouse liver cDNA library, E1-deleted recombinant adenovirus expressing the Homer protein (Adv.CMV.mHomer-2a) was constructed to determine its physiological function in peripheral tissues. Adv.CMV.mHomer2a, but not Adv.CMV.LacZ (recombinant adenovirus expressing beta-galactosidase), strongly inhibited the growth rate of HUVECs (human umbilical vein endothelial cells) probably via inducing apoptosis determined by acridine orange/ethidium bromide (AO/EB) staining methods. This study suggests that the Homer gene is present in human specimens in the involuting phase of hemangioma, and it might be involved in the growth control.
Subject(s)
Adolescent , Adult , Animals , Child , Child, Preschool , Female , Humans , Male , Mice , Middle Aged , Rats , Apoptosis , Base Sequence , Blood Vessels/abnormalities , Carrier Proteins/genetics , Cells, Cultured , DNA, Complementary/genetics , Endothelium, Vascular/cytology , Hemangioma/blood supply , Neuropeptides/genetics , Reverse Transcriptase Polymerase Chain Reaction , Skin/blood supply , Skin Neoplasms/blood supplyABSTRACT
Recent study showed that peripheral inflammation induced an increased expression of brain-derived neurotrophic factor (BDNF) mRNA which was mediated by nerve growth factor in the dorsal root ganglion (DRG). Therefore, it is conceivable that peripheral inflammation may induce an increase in BDNF synthesis in DRG and consequently enhance the level of BDNF in the spinal cord and that gene expression of trkB mRNA may be altered. In the present study, we evaluated changes in BDNF-immunoreactivity and trkB mRNA in the DRG and spinal cord by means of immunohis-tochemistry and RT-PCR, respectively, following peripheral tissue inflammation produced by intraplantar injection of Freund's adjuvant into rat paws. In addition, coexistence of BDNF and preprotachykinin (PTT) mRNAs, BDNF and CGRP mRNAs or BDNF and trkB mRNAs in the DRG following inflammation was observed by means of in situ hybridization. The results obtained were as follows; 1. Inflammation induced a significant increase of the number of BDNF-immunoreactive (IR) neurons in the ipsilateral DRGs. The increase was observed 1 and 3 days after injection of adjuvant, and the levels had returned to normal by 7 days. In the spinal cord, inflammation also induced an elevation in the expression of BDNF-IR terminals in the medial superficial layers of the ipsilateral dorsal horn and in lamina V 1 and 3 days after injection. 2. There was significant increase of truncated trkB (t-trkB) mRNA in the ipsilateral DRG 3 days following inflammation. Changes in the expression of trkB mRNA in the DRG or trkB and t-trkB mRNAs in the spinal cord were not observed. 3. Many neurons showed increased coexistence of BDNF and PTT mRNAs or BDNF and CGRP mRNAs in the DRG following inflammation. 4. Few neurons showed coexistence of BDNF and trkB mRNAs in the DRG following inflammation. The results suggest a paracrine function for BDNF within the DRG in addition to an important role related with nociception following peripheral inflammation.