Isoprostanes, prostaglandins and tocopherols in pre-eclampsia, normal pregnancy and non-pregnancy

This study is designed to evaluate whether oxidative stress and inflammation are involved in severe pre-eclampsia compared to normal pregnancy and non-pregnancy. We have measured plasma and urinary levels of 8-iso-PGF2alpha, a major isoprostane as an indicator of oxidative stress; plasma and urinary 15-keto-dihydro-PGF2alpha, a major metabolite of cyclooxygenase-catalysed PGF2alpha as an indicator of inflammatory response, and plasma -alpha-and -gamma-tocopherol in 18 pre-eclamptic, 19 normal pregnancy and 20 non-pregnant women. Pregnant women had significantly higher levels of 8-iso-PGF2alpha and PGF2alpha metabolite as compared to the non-pregnancy. Levels of 8-iso-PGF2alpha in the pre-eclamptic women did not differ from the normal pregnancy but PGF2alpha metabolite levels were significantly higher in normal pregnancy. On the other hand, gamma-tocopherol levels were significantly lower in pre-eclampsia than normal pregnancy. In contrast, the concentration of alpha-tocopherol was very similar between the groups. alpha-and gamma-tocopherol levels were significantly lower in pregnancy compared to non-pregnancy. Although no direct evidence of oxidative stress and inflammatory response was observed in severe pre-eclampsia, a reduction of gamma-tocopherol suggests the possible precedence of oxidative stress in this condition. Higher levels of isoprostanes and prostaglandin metabolite in late pregnancy suggest the importance of both free radicals and cyclooxygenase-catalysed oxidation products in normal biological processes of pregnancy.     

The chemokine receptor CCR5 is not a necessary inflammatory mediator in kainic acid-induced hippocampal injury: evidence for a compensatory effect by increased CCR2 and CCR3

Chemokines and their receptors have been strongly implicated in the inflammatory process. However, their roles in excitotoxic brain injury are largely unknown. In this study we used C-C chemokine receptor 5 (CCR5) knockout (KO) mice to investigate the role of CCR5 in neurodegeneration induced by intranasal administration of the excitotoxin kainic acid (KA). Although KA treatment resulted in an increased CCR5 mRNA level in the hippocampi of wild-type mice, a CCR5 deficiency in KO mice did not affect either the clinical and pathological changes in vivo or the neuronal susceptibilities to KA insult in vitro. KA treatment stimulated mRNA expression of the monocyte chemoattractant protein-2 (MCP-2) in both the wild-type and KO mice. KA treatment did not affect mRNA levels for the macrophage inflammatory protein-1alpha (MIP-1alpha) or the regulated upon activation normal T cells expressed and secreted protein (RANTES) in either wild-type or CCR5 KO mice. CCR2 mRNA expression was undetectable in the hippocampi of wild-type mice regardless of KA treatment. In contrast, CCR5 KO mice showed CCR2 mRNA expression that was remarkably increased after KA treatment. KA treatment did not affect CCR3 mRNA expression in the wild-type mice, whereas KO mice showed both a higher basal level of CCR3 mRNA expression as well as a strong upregulation following KA treatment. These results indicate that CCR5 is not a necessary inflammatory mediator in KA induced neurodegeneration. The roles of CCR5 in excitotoxic injury in CCR5 deficient mice are compensated by increased CCR2 and CCR3 expression, which share the common MCP-2 ligand with CCR5.     

A phospholipase D-dependent process forms lipid droplets containing caveolin,adipocyte differentiation-related protein,and vimentin in a cell-free system

We developed a microsome-based, cell-free system that assembles newly formed triglyceride (TG) into spherical lipid droplets. These droplets were recovered in the d 相似文献   

Patterned gene programs and target remodeling following axotomy at a major site for sensory innervation

The genetic mechanisms that a target uses to reestablish the connections of regenerating axons were explored using oligonucleotide microarrays and real-time PCR. In normal and denervated mouse vibrissa follicles, patterns of genetic regulation were assessed in adjacent targets that normally receive different types of sensory and autonomic innervation. We show that a target remodeling occurs following axotomy involving reduced hair growth, altered hair follicle integrity and remodeling of the extracellular matrix. Also, we found two orphan receptors putatively involved in hair growth. Our data further demonstrate region-specific regulation of genes putatively involved in target-axon interactions. Thus, this study shows for the first time that major target remodeling occurs following denervation and suggests putative functions for several novel genes.     

Cyclooxygenase-1 and cyclooxygenase-2 expression in rat kidney and adrenal gland after stimulation with systemic lipopolysaccharide

Cyclooxygenase-2 (COX-2) is a recently discovered isoform of cyclooxygenase that is inducible by various types of inflammatory stimuli. Although this enzyme is considered to play a major role in inflammation processes by catalyzing the production of prostaglandins, the precise location, distribution, and regulation of prostaglandin synthesis remains unclear in several tissues. Using in situ hybridization histochemistry, we investigated the induction of COX-1 and COX-2 mRNA expression after systemic administration of a pyrogen, lipopolysaccharide (LPS), in kidney and adrenal gland in the rat. The COX-2 mRNA signals dramatically increased 1 h after LPS treatment in the kidney outer medulla and adrenal cortex, where almost no or little expression was observed in nontreated animals, and returned to control levels within 24 h. COX-2 mRNA levels increased in the kidney inner medulla 6 h after treatment. There was also a significant increase in mRNA levels in the kidney cortex and adrenal medulla. On the other hand, COX-1 mRNA levels did not show any detectable changes except in the kidney inner medulla, where a significant downregulation of mRNA expression was observed after LPS treatment. Light and electron immunocytochemistry using COX-2 antibodies showed that strong COX-2 immunoreactivity was localized to certain cortical cells of the thick ascending limb of Henle. In addition, based on double-staining with antiserum to nitric oxide synthase (NOS) four further cell populations could be identified in kidney cortex, including weakly COX-2-positive, NOS-positive macula densa cells. After LPS treatment, changes in COX-2 immunoreactivity could be observed in interstitial cells in the kidney medulla and in inner cortical cells in the adrenal gland. These results show that COX-2 is a highly induced enzyme that can be up-regulated in specific cell populations in kidney and adrenal gland in response to inflammation, leading to the elevated levels of prostaglandins seen during fever. In contrast COX-1 mRNA levels remained unchanged in this experimental situation, except for a decrease in kidney inner medulla.     

Bioenergetics of <Emphasis Type="Italic">Yarrowia lipolytica</Emphasis> Cells Grown at Alkaline Conditions

Energy status of the novel alkalitolerant Yarrowia lipolytica yeast strain grown at alkaline conditions (pH 9.7) was examined. Cells grown under such severe conditions were found to preserve high respiratory activity. The oxidative phosphorylation system dominated in the energy budget of the cell. A procedure was specially design to isolate tightly coupled mitochondria from yeast cells grown at alkaline conditions. The isolated mitochondrial preparations met known criteria of physiological intactness, as inferred from their ability to maintain distinctive state 4–3 respiration transition upon addition of ADP, high respiratory rates, good respiratory control values, and ADP/O ratios close to the theoretically expected maxima for the substrates used.     

The effects of 884 MHz GSM wireless communication signals on headache and other symptoms: an experimental provocation study

Findings from prior studies of possible health and physiological effects from mobile phone use have been inconsistent. Exposure periods in provocation studies have been rather short and personal characteristics of the participants poorly defined. We studied the effect of radiofrequency field (RF) on self-reported symptoms and detection of fields after a prolonged exposure time and with a well defined study group including subjects reporting symptoms attributed to mobile phone use. The design was a double blind, cross-over provocation study testing a 3-h long GSM handset exposure versus sham. The study group was 71 subjects age 18-45, including 38 subjects reporting headache or vertigo in relation to mobile phone use (symptom group) and 33 non-symptomatic subjects. Symptoms were scored on a 7-point Likert scale before, after 1(1/2) and 2(3/4) h of exposure. Subjects reported their belief of actual exposure status. The results showed that headache was more commonly reported after RF exposure than sham, mainly due to an increase in the non-symptom group. Neither group could detect RF exposure better than by chance. A belief that the RF exposure had been active was associated with skin symptoms. The higher prevalence of headache in the non-symptom group towards the end of RF exposure justifies further investigation of possible physiological correlates. The current study indicates a need to better characterize study participants in mobile phone exposure studies and differences between symptom and non-symptom groups.     

Lactate and epinephrine during exercise in altitude natives

Kayser, Bengt, Roland Favier, Guido Ferretti, DominiqueDesplanches, Hilde Spielvogel, Harry Koubi, Brigitte Sempore, and HansHoppeler. Lactate and epinephrine during exercise in altitudenatives. J. Appl. Physiol. 81(6):2488-2494, 1996.We tested the hypothesis that the reported lowblood lactate accumulation ([La]) during exercise inaltitude-native humans is refractory to hypoxia-normoxia transitions byinvestigating whether acute changes in inspiredO₂ fraction(FI_O2) affect the[La] vs. power output ()relationship or, alternatively, as reported for lowlanders, whetherchanges in [La] vs. on changes inFI_O2 are related tochanges in blood epinephrine concentration ([Epi]). Altitude natives [n = 8, age 24 ± 1 (SE) yr, body mass 62 ± 3 kg, height 167 ± 2 cm]in La Paz, Bolivia (3,600 m) performed incremental exercise with twolegs and one leg in chronic hypoxia and acute normoxia (AN). Submaximalone- and two-leg O₂ uptake (O₂) vs. relationships were not altered byFI_O2. AN increased two-legpeak O₂ by 10% and peak by 7%. AN paradoxically decreasedone-leg peak O₂ by 7%,whereas peak remained the same. The[La] vs. relationships were similar tothose reported in unacclimatized lowlanders. There was a shift to theright on AN, and maximum [La] was reduced by 7 and 8% forone- and two-leg exercises, respectively. [Epi] and[La] were tightly related (mean r = 0.81) independently ofFI_O2. Thus normoxiaattenuated the increment in both [La] and [Epi]as a function of , whereas the correlation between[La] and [Epi] was unaffected. These data suggest loose linkage of glycolysis to oxidative phosphorylation under influence from [Epi]. In conclusion, high-altitudenatives appear to be not fundamentally different from lowlanders with regard to the effect of acute changes inFI_O2 on [La] during exercise.

     

Structural studies of the manganese stabilizing subunit in photosystem II

Photosystem II (PSII) is the plant photosynthetic reaction center that carries out the light driven oxidation of water. The water splitting reactions are catalyzed at a tetranuclear manganese cluster. The manganese stabilizing protein (MSP) of PSII stabilizes the manganese cluster and accelerates the rate of oxygen evolution. MSP can be removed from PSII, with an accompanying decrease in activity. Either an Escherichia coli expressed version of MSP or native, plant MSP can be rebound to the PSII reaction center; MSP reconstitution reverses the deleterious effects associated with MSP removal. We have employed Fourier transform infrared (FTIR) spectroscopy and solution small angle x-ray scattering (SAXS) techniques to investigate the structure of MSP in solution and to define the structural changes that occur before and after reconstitution to PSII. FTIR and SAXS are complementary, because FTIR spectroscopy detects changes in MSP secondary structure and SAXS detects changes in MSP size/shape. From the SAXS data, we conclude that the size/shape and domain structure of MSP do not change when MSP binds to PSII. From FTIR data acquired before and after reconstitution, we conclude that the reconstitution-induced increase in beta-sheet content, which was previously reported, persists after MSP is removed from the PSII reaction center. However, the secondary structural change in MSP is metastable after removal from PSII, which indicates that this form of MSP is not the lowest energy conformation in solution.