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Journal Article 2011; 32(3): 313-316 PubMed PMID: 21712774 Citation  Keywords:  Amyloid Precursor Protein Secretases:biosynthesis, Amyloid beta-Peptides:biosynthesis, Amyloid beta-Protein Precursor:biosynthesis, Aspartic Acid Endopeptidases:biosynthesis, Cell Line, Cells, Cultured, DNA:biosynthesis, Humans, Luciferases:genetics, RNA,.   

OBJECTIVE: The effect of SUMO on the promoter activity and mRNA expression of BACE gene was investigated to find the connection between sumoylation and APP processing.

METHODS: The BACE promoter activity was measured by reporter gene analysis and BACE mRNA level was investigated using real-time RT-PCR method.

RESULTS: BACE gene promoter activity was inhibited by the over-expression of SUMO proteins and was blocked by disrupting the SP1 site. Endogenous BACE mRNA level was also negatively regulated by the induction of SUMO proteins. Using a specific inhitor of SP1, BACE promoter activity was coordinately inhibited.

CONCLUSIONS: SUMO negatively regulates the BACE expression and SP1 is involved in the process....

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Journal Article 2011; 32(2): 212-219 PubMed PMID: 21552195 Citation  Keywords:  Animals, Gastric Mucosa:cytology, Gastrointestinal Tract:cytology, Male, Models, Animal, Neuropeptide Y:metabolism, Obesity:metabolism, Pancreatic Polypeptide:metabolism, Receptors, Cell Surface:metabolism, Receptors, Neuropeptide Y:metabolism, Shrews,.   

OBJECTIVES: To investigate the immunolocalization of the pancreatic polypeptide (PP)-fold peptide family, important regulatory factors for food intake, in the gastrointestinal tract of Suncus murinus, and to discuss the relation with the obesity-resistance, visceral fat accumulation-resistance phenomenon in Suncus murinus.

METHODS: The gastrointestinal tract of adult Suncus murinus, except for the stomach and pylorus, was divided into five sections (S1, corresponding to the duodenum, S2, S3 and S4, corresponding to the jejunum and ileum, and S5, corresponding to the colon and rectum in other mammals), to investigate the PP family and their receptor-producing cells by means of immunohistochemistry.

RESULTS: NPY, PYY, Y1 and Y4-immunoreactive cells were distributed widely throughout the gastrointestinal tract, moreover, the PP family and their receptor-immunoreactive cells were predominantly distributed at the end of the gastrointestinal tract, the rectum.

CONCLUSION: In this study, we investigated the distribution of the PP family and their receptor-producing cells in the gastrointestinal tract of Suncus murinus in detail for the first time. It was presumed that the wide distribution of Y4 in the gastrointestinal tract may be related to (associated with) the phenomenon of natural obesity-resistance, visceral fat accumulation-resistance in aging Suncus murinus....

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Journal Article 2010; 31(5): 609-615 PubMed PMID: 21173750 Citation  Keywords:  Animals, Disease Models, Animal, Immunohistochemistry, Injections, Intraperitoneal, Injections, Intraventricular, Interleukin-1beta, Lipopolysaccharides, Male, Neuronal Plasticity, Neuropeptides:biosynthesis, Paraventricular Hypothalamic Nucleus:immunolog.   

OBJECTIVES AND METHODS: Neuropeptides, as the main neuroendocrine system effectors, regulate notably the response to different stressors via a secretory plasticity within their respective hypothalamic neuronal populations. The aim of the present study was to explore by immunocytochemistry the occurrence and the potential expression plasticity of the novel neuropeptide EM66 in the CRH neurones of stressed rats.

RESULTS: The secretogranin II (SgII)-derived peptide EM66 is strongly expressed within hypothalamic neuroendocrine areas such as the parvocellular aspect of the paraventricular nucleus (pPVN) as well as the median eminence, suggesting a probable hypophysiotropic effect of this peptide. As a first approach to investigate such a role, we evaluated by immunohistochemistry EM66 expression within the pPVN following acute immune stress induced by lipopolysaccharide (LPS) or interleukin-1β (IL-1β) injection in rat. This study showed that EM66 is present in the pPVN but the number of EM66 immunolabeled cells did not fluctuate in this structure following LPS peripheral injection. In line with this observation, an intracerebroventricular injection of IL-1β did not provoke any significant variation of the number of intraparaventricular EM66 neurones.

CONCLUSION: The present data revealed for the first time that EM66 expression would be insensitive to the central and peripheral cytokines within the neurosecretory hypothalamic pPVN. This result indicates that EM66 does not participate to the phenotypic plasticity of hypothalamic parvicellular neurones in response to acute inflammatory stress....

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Journal Article 2010; 31(2): 198-202 PubMed PMID: 20424589 Citation  Keywords:  Animals, Body Temperature, Fasting:adverse effects, Fibroblast Growth Factors:deficiency, Hypothalamus:metabolism, Hypothermia:etiology, Ketogenic Diet:methods, Liver:metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Motor Activity, Neuropeptide.   

BACKGROUND: Fibroblast growth factor 21 (FGF21) is a key metabolic regulator that is induced by peroxisome proliferator-activated receptor alpha (PPARalpha) activation in response to fasting. We recently reported that bezafibrate, a pan-agonist of PPARs, decreases body temperature late at night through hypothalamic neuropeptide Y (NPY) activation and others have shown that mice overexpressing FGF21 are prone to torpor.

OBJECTIVES: We examined whether FGF21 is essential for fasting-induced hypothermia using FGF21 knockout (KO) mice.

RESULTS: Acute fasting decreased body temperature late at night accompanied by the induction of hepatic FGF21 and hypothalamic NPY expression in wild-type mice. A deficiency of FGF21 affected neither fasting-induced hypothermia nor hypothalamic NPY induction. Fasting enhanced locomotor activity in both genotypes. On the other hand, a deficiency of FGF21 significantly attenuated chronic hypothermia and hypoactivity induced by a ketogenic diet (KD).

CONCLUSIONS: Our findings suggest that FGF21 is not essential for the hypothermia that is associated with the early stages of fasting, although it might be involved in the adaptive response of body temperature to chronic starvation....

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Journal Article 2010; 31(1): 103-112 PubMed PMID: 20150881 Citation  Keywords:  Animals, Female, GABA Antagonists:pharmacology, Ganglia, Sympathetic:drug effects, Gonadal Hormones:secretion, Nerve Growth Factor:metabolism, Neuropeptides:pharmacology, Nitric Oxide:metabolism, Nitric Oxide Synthase Type II:metabolism, Norepinephrine:ph.   

OBJECTIVE: Ovarian steroids are modulated by neural influences. In this work we investigate whether norepinephrine (NE) modifies the vasoactive intestinal peptide (VIP) or neuropeptide Y (NPY) actions in coeliac ganglion (CG) on the ovarian hormone release, and evaluate the participation of nitric oxide (NO), measured as nitrite, and of inducible nitric oxide synthetase (iNOS) protein, nerve growth factor (NGF) and its trkA receptor gene expression in the ovarian response.

METHODS: The study was performed in the ex vivo CG-superior ovarian nerve (SON)-ovary system of rats on diestrus day 2 (D2). CG and ovary were placed in separate compartments connected by the SON and incubated with Krebs-Ringer buffer. After addition of 50 ng/ml VIP, 50 ng/ml NPY, 10-6 M NE, or a mix of VIP+NE or NPY+NE in ganglion, samples from the ovarian compartment were taken at different times throughout 180 minutes to measure progesterone, androstenedione and nitrite levels.

RESULTS: VIP and NPY in ganglion induced an increase of progesterone release that was associated for VIP, but not NPY, with a decrease of ovarian nitrite levels, iNOS protein, and NGF/trkA receptor mRNA expression. By contrast, NE in ganglion decreased progesterone, an effect that was suppressed by addition of propranolol in ganglion, and increased nitrites/iNOS and NGF/trkA receptor expression in ovary. GABA A receptor antagonist bicuculline (20 muM) added in ovarian compartment prevented the inhibitory effect on progesterone caused by NE in CG. Androstenedione was not modified under neuropeptides or NE ganglionic stimulation.

CONCLUSIONS: Finally, results from VIP+NE or NPY+NE in ganglion showed that ovarian response on D2 induced by VIP or NPY alone is moderated by the opposite action of NE, and occurs only on progesterone, the most sensitive steroid to neural action....

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Journal Article 2010; 31(1): 97-102 PubMed PMID: 20150879 Citation  Keywords:  Age of Onset, Case-Control Studies, Depressive Disorder:epidemiology, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Intracellular Signaling Peptides and Proteins, Male, Memory Disorders:genetics, Phosphoproteins, Polymorphis.   

OBJECTIVE: Depression is a disease of multifactor background. Episodic memory dysfunction is one of depression characterising disturbances, which may lead to its onset and development. Memory processes are controlled by a number of extra- and intracellular mechanisms. KIBRA, a newly discovered protein, belonging to signal transduction proteins, participates in the control of episodic memory. The presented study was designed to assess correlation between single nucleotide polymorphism (SNP) T/C (rs17070145) of the KIBRA gene and the risk of recurrent depressive disorder (DD).

METHODS: The study was carried out in a group of 181 patients with recurrent DD and 149 healthy control subjects. Genotyping was conducted by polymerase chain reaction (PCR)/restriction fragment length polymorphism (RLFP) method.

RESULTS: TThe obtained results have revealed no significant correlation between the studied polymorphism and recurrent DD. Obtained value of the disease odds ratio (ORdis) suggests that presence of T/T homozygote decreases risk of development of recurrent DD, but the result was not statistically significant.

CONCLUSIONS: Following the results, it may be concluded that the studied polymorphism does not influence either the onset mechanism or the course of recurrent DD. Even if T/C polymorphism of the KIBRA gene induces memory disturbances, they may be unspecific and unselective for recurrent DD. Further studies on the genes, which control characteristic processes of DD and influence their course, are demanded and mostly justified....

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Journal Article 2010; 31(1): 63-66 PubMed PMID: 20150869 Citation  Keywords:  Case-Control Studies, Cystinyl Aminopeptidase:blood, Down-Regulation, Enzyme Activation, Female, Gestational Age, Humans, Pre-Eclampsia:blood, Pregnancy, Premature Birth:blood, Severity of Illness Index, Term Birth:blood,.   

OBJECTIVE: Placental Leucine Aminopeptiadse (P-LAP) also known as oxytocinase, is secreted by syncytiotrophoblast and increases gradually during pregnancy until delivery. It is a regulator of uterine contractions, of vascular resistance and of volume of the retroplacental blood pool. Recently, it was shown that it could also regulate metalloproteinase 9 activity and thus, invasiveness of trophoblastic cells. Since development of preeclampsia could be initiated by decreased cytotrophoblastic invasion of spiral arterioles and a reduced uteroplacental perfusion, we speculate that circulating P-LAP activity could be decreased during preeclampsia.

MATERIALS AND METHODS: Case-control study was evaluated in 84 women. P-LAP activity was measured in n=51 healthy pregnant women at term, and compared with n=16 normotensive women delivering preterm and n=17 women diagnosed with pre-eclampsia. P-LAP activity was determined by colorimetry in plasma samples using L-Leucine-p-nitroanilide as substrate.

RESULTS: P-LAP activity was significantly lower in sera of preeclamptic women (0.91+/-0.122 mDO/min) as compared to normotensive controls (1.41+/-0.103 mDO/min; p=0.003) irrespective of time of delivery.

CONCLUSIONS: These findings confirm the probable involvement of P-LAP in trophoblast invasion and development of preeclampsia....

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Comparative Study 2009; 30(1): 46-50 PubMed PMID: 19300398 Citation  Keywords:  Amyloid beta-Peptides:blood, Animals, Brain:metabolism, Guinea Pigs, Kidney:metabolism, Male, Orchiectomy, Testosterone:metabolism, Time Factors,.   

OBJECTIVES: The association between low testosterone levels and Alzheimer's disease (AD) amyloid beta-peptide (Abeta) metabolism was investigated in brain and kidney of guinea pigs.

METHODS: The expression of Abeta peptide in the brain and kidney was assessed by using the immunohistochemistry method.

RESULTS: No expression of Abeta was seen in both groups of animals. This negative staining was found until the fourth week following castration. The formation of Abeta in guinea pigs is perhaps not a short duration process and may undergo different metabolic pathway compare to humans.

CONCLUSION: castration was not associated with the formation of Abeta in the brain and kidneys during a 1-month period and might require a longer period of time....

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