Presenilin-1 (PS1) and presenilin-2 (PS2), the major genes of familial Alzheimer's disease, are homologous to sel-12, a Caenorhabditis elegans gene involved in cell fate decision during development. Recently, wild-type and mutant presenilins have been associated also with apoptotic cell death. By using stable transfection of antisense cDNAs, we studied the functions of PS1 and PS2 during neuronal differentiation in the NTera2 human teratocarcinoma (NT2) cell line. Expression of antisense PS1 resulted in a failure of the clones to differentiate into neurons after retinoic acid induction, whereas cells transfected with antisense PS2 differentiated normally. Concomitantly, antisense PS1 clones were associated with increased apoptosis both under basal conditions and during the early period of neuronal differentiation after retinoic acid treatment. Overexpression of bcl-2 in antisense PS1 clones reduced cell death and resulted in a recovery of neuronal differentiation. These studies suggest that PS1 plays a role in differentiation and cell death and that PS1 and PS2 have differing physiological roles in this experimental paradigm.

Introduction: The purpose of this study was to investigate the effects of 12-week exercise training on circulating retinol-binding protein 4 (RBP4) concentration and cardiovascular disease (CVD) risk factors in obese men. Methods: 29 obese men (age 48 ± 2 years; BMI 29.6 ± 0.7 kg/m²) participated in a 12-week exercise program (50–70% maximal heart rates; 3 times/week) without calorie restriction. Anthropometric parameters, CVD risk factors (total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol, triglycerides (TG), and quantitative insulin sensitivity check index), and circulating RBP4 and adipokine (adiponectin, leptin, and interleukin-6 (IL-6)) concentrations were measured. Results: Exercise training significantly improved in absolute peak oxygen consumption (p < 0.05), and CVD risk factors (p < 0.05), with the exception of HDLC. There was a significant decrease in circulating RBP4, leptin, and IL-6 concentrations (p < 0.05). Stepwise regression analysis revealed that changes in RBP4 concentration were independently related to the changes in TG concentration (β = 0.46, p < 0.05). Conclusion: These results demonstrate that exercise training without calorie restriction improves several CVD risk factors and circulating RBP4 and adipokine concentrations. Moreover, the change in circulating RBP4 may be more associated with the improvements in TG concentration in obese men.

Aim: Enhancement of lipoprotein lipase (LPL) activity through drug administration has been shown to increase pre-heparin serum LPL concentrations; however, pre-heparin serum LPL responses to exercise training have not been determined. The present study was undertaken to investigate the effects of 12 weeks of supervised aerobic exercise training on pre-heparin serum LPL concentrations in overweight/obese men. Methods: Fifteen overweight/obese middle-aged men were assigned to one of two 12-week supervised exercise interventions: a walking group (eight participants gradually increasing brisk walking to 60 min/day 3 days a week) or a jogging group (seven participants gradually increasing jogging to 60 min/day 3 days a week). All participants maintained ad libitum diets. Blood samples were collected at baseline and immediately after 12 weeks. The primary outcome was pre-heparin serum LPL. Results: Pre-heparin serum LPL concentrations were increased in the jogging group after 12 weeks compared with the baseline values (mean SEM: 37.6 4.7 vs. 51.0 6.6 ng/mL, respectively, p 0.033). In the walking group, pre-heparin serum LPL concentrations remained unchanged after 12 weeks. Conclusions: This study demonstrates that 12 weeks of jogging training increases pre-heparin serum LPL concentrations in overweight/obese middle-aged men. J Atheroscler Thromb, 2010; 17:21-29.Key words; Aerobic exercise, Training, Pre-heparin serum lipoprotein lipase, Lipid metabolism nous injection of heparin, LPL is detached from the endothelium surface and released in blood. Alternatively, a small fraction of LPL protein naturally (i.e., without intravenous injection of heparin) detached from the endothelial surface is detectable in serum by a sensitive enzyme-linked immunoassay 2,3) . Although pre-heparin serum LPL is catalytically inactive and its physiological role is not fully understood, previous cross-sectional studies have shown that pre-heparin serum LPL concentrations were considerably lower in patients with type 2 diabetes 4) and hyperlipidaemia 5) compared with healthy individuals. A previous cross-sectional study also reported an inverse relationship between pre-heparin serum LPL concentration and serum triacylglycerol concentration in both healthy individuals and hyperlipidaemic patients 6)

Circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has been reported to be associated with acute coronary syndrome, but its association with obesity has not been elucidated. In this study, we examined whether weight reduction would reduce the serum levels of sLOX-1 in a 12-week weight reduction intervention. Thirty-eight overweight middle-aged men were enrolled in the study, and 32 completed the intervention. The serum level of sLOX-1 was measured using a chemiluminescent enzyme-linked immunoassay. After the intervention program, body weight and the serum level of sLOX-1 decreased significantly (-7.5% +/- 4.8% and -72.1% +/- 35.9%, respectively). Changes in serum levels of sLOX-1 were positively correlated with changes in body weight (r = 0.54, P = .003), body mass index (r = 0.57, P = .001), body fat mass (r = 0.57, P = .002), total cholesterol (r = 0.41, P = .03), subcutaneous fat area (r = 0.50, P = .007), high-sensitivity C-reactive protein (r = 0.56, P = .002), leptin (r = 0.47, P = .01), and tumor necrosis factor-alpha (r = 0.32, P = .09); but no correlations were observed with fasting glycemic-related factors (blood glucose, hemoglobin A(1c), and insulin). Changes in body mass index and high-sensitivity C-reactive protein were selected as significant predictors of sLOX-1 changes by multiple regression analyses. These results suggest that LOX-1 induction may be related to adipocyte metabolism, inflammation, and immune response associated with obesity.

SUMMARY. Serum amyloid A protein (SAA) is a sensitive acute phase reactant. We developed a method for the rapid measurement of human SAA in serum by kinetic nephelometry of anti-SAA antibody-coated latex agglutination. Measurement takes lessthan 6 min using an automated analyser. Standardization of the assay employs SAA-enriched high density lipoprotein as the primary standard. The values determined by our new method and by conventional enzymeimrnunoassay showed good agreement (r=0·988). The normal range was 0'17-10'0 mg/L [mean (SD)]. This rapid method should prove useful in clinical laboratories.