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3β-Hydroxysteroid-Δ24 reductase (DHCR24) is an endoplasmic reticulum (ER)-localized multifunctional enzyme that possesses anti-apoptotic and cholesterol-synthesizing activities. Accumulating evidence suggests that ER stress is involved in the pathogenesis of neurodegenerative disease. In this study, we investigated whether DHCR24 may function as a neuroprotective protein under ER stress. Neuroblastoma N2A cells were infected with adenovirus expressing myc-tagged DHCR24 (Ad-DHCR24) or lacZ (Ad-lacZ, serving as a control) and subjected to ER-stress, induced with Tunicamycin (TM). Cells infected with Ad-DHCR24-myc were resistant to TM-induced apoptosis, and showed weaker level of caspase-12 activity. These cells also exhibited lower levels of Bip and CHOP proteins than Ad-LacZ-infected cells. Moreover, a stronger and rapid activation of PERK, and a prolonged activation of JNK and p38 were observed in Ad-LacZ-infected cells. The generation of intracellular reactive oxygen species from ER stress was also diminished by the overexpression of DHCR24. Additionally, intracellular cholesterol level was also elevated in the Ad-DHCR24-infected cells, accompanied by a well-organized formation of caveolae (cholesterol-rich microdomain) on the plasma membrane, and improved colocalization of caveolin-1 and insulin-like growth factor 1 receptor. These results demonstrated for the first time that DHCR24 could protect neuronal cells from apoptosis induced by ER stress.

We monitored soil respiration (Rs), soil temperature (T) and volumetric water content (VWC%) over four years in one typical conventional and four alternative cropping systems to understand Rs in different cropping systems with their respective management practices and environmental conditions. The control was conventional double-cropping system (winter wheat and summer maize in one year--Con.W/M). Four alternative cropping systems were designed with optimum water and N management, i.e. optimized winter wheat and summer maize (Opt.W/M), three harvests every two years (first year, winter wheat and summer maize or soybean; second year, fallow then spring maize--W/M-M and W/S-M), and single spring maize per year (M). Our results show that Rs responded mainly to the seasonal variation in T but was also greatly affected by straw return, root growth and soil moisture changes under different cropping systems. The mean seasonal CO2 emissions in Con.W/M were 16.8 and 15.1 Mg CO2 ha(-1) for summer maize and winter wheat, respectively, without straw return. They increased significantly by 26 and 35% in Opt.W/M, respectively, with straw return. Under the new alternative cropping systems with straw return, W/M-M showed similar Rs to Opt.W/M, but total CO2 emissions of W/S-M decreased sharply relative to Opt.W/M when soybean was planted to replace summer maize. Total CO2 emissions expressed as the complete rotation cycles of W/S-M, Con.W/M and M treatments were not significantly different. Seasonal CO2 emissions were significantly correlated with the sum of carbon inputs of straw return from the previous season and the aboveground biomass in the current season, which explained 60% of seasonal CO2 emissions. T and VWC% explained up to 65% of Rs using the exponential-power and double exponential models, and the impacts of tillage and straw return must therefore be considered for accurate modeling of Rs in this geographical region.

Leptin acts on the ventral tegmental area (VTA) to modulate neuronal function and feeding behavior in rats and mice. To identify the intracellular effectors of the leptin receptor (Lepr), downstream signal transduction events were assessed for regulation by direct leptin infusion. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) and phosphorylated extracellular signal-regulated kinase-1 and -2 (pERK1/2) were increased in the VTA while phospho-AKT (pAKT) was unaffected. Pretreatment of brain slices with the mitogen-activated protein kinase kinase -1 and -2 (MEK1/2) inhibitor U0126 blocked the leptin-mediated decrease in firing frequency of VTA dopamine neurons. The anorexigenic effects of VTA-administered leptin were also blocked by pretreatment with U0126, which effectively blocked phosphorylation of ERK1/2 but not STAT3. These data demonstrate that pERK1/2 may have a critical role in mediating both the electrophysiogical and behavioral effects of leptin receptor signaling in the VTA. [ABSTRACT FROM AUTHOR]

Leptin acts on the ventral tegmental area (VTA) to modulate neuronal function and feeding behavior in rats and mice. To identify the intracellular effectors of the leptin receptor (Lepr), downstream signal transduction events were assessed for regulation by direct leptin infusion. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) and phosphorylated extracellular signal-regulated kinase-1 and -2 (pERK1/2) were increased in the VTA while phospho-AKT (pAKT) was unaffected. Pretreatment of brain slices with the mitogen-activated protein kinase kinase -1 and -2 (MEK1/2) inhibitor U0126 blocked the leptin-mediated decrease in firing frequency of VTA dopamine neurons. The anorexigenic effects of VTA-administered leptin were also blocked by pretreatment with U0126, which effectively blocked phosphorylation of ERK1/2 but not STAT3. These data demonstrate that pERK1/2 may have a critical role in mediating both the electrophysiogical and behavioral effects of leptin receptor signaling in the VTA.