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[Rat tissues antioxidant status correction by peptide delta sleep during physiological aging of the organism].
Adv Gerontol
T I Bondarenko, D S Kutilin, I I Mikhaleva
It is shown that exogenous delta-sleep inducing peptide increases glutathione antioxidant system level in rat tissues at different stages of ontogenesis, by subcutaneous injection to rats 2-24 months postnatal development in a dose of 100 mg/kg animal body weight by courses of 5 consecutive days per month, and this effect is especially marked in non-renewable postmitotic tissues.
[The role of NMDA and NK1 receptors in cardiac nociceptive information transmissions in the spinal cords of rats].
Sichuan Da Xue Xue Bao Yi Xue Ban
Ling-Heng Kong, Na Sun, Juan-Xia Zhu +3 more
To determine the effects of NMDA and NK1 receptor agonist and antagonist on the EMG and the synaptic mechanism of nociceptive information transmissions in the spinal cords.
Association of HSL gene E1-c.276C>T and E8-c.51C>T mutation with economical traits of Chinese Simmental cattle.
Mol Biol Rep
X B Fang, L P Zhang, X Z Yu +4 more
Hormone-sensitive lipase (HSL) is responsible for the decomposition of triglycerides in adipose tissue to release free fatty acids, and it is a key rate-limiting enzyme in the regulation of adipose tissue deposition and decomposition. The objective of this study was to evaluate the association between novel SNPs in the coding region of bovine HSL gene and carcass and meat quality traits of Chinese Simmental-cross steers. Two novel SNPs were genotyped and the 47 traits of carcass and meat quality traits were measured in the population studied. Statistical analysis revealed that the SNPs of HSL gene were associated with the carcass and meat quality traits. The individuals with TT genotypes of E1-276C>T showed significant higher dressing percentage, net meat rate, hind legs circumference, fat coverage rate, mesenteric fat and kidney fat (p < 0.05). E8-51C>T (P17S) also showed a significant association with the pH of beef and fatty acids content in Chinese Simmental cattle (p < 0.01). Our findings indicated that polymorphisms in HSL might be one of important genetic factors that influence carcass yield and meat quality in beef cattle, and it may be a useful marker for meat quality traits in future marker-assisted selection programs in beef cattle breeding and production.
Differential involvement of signaling pathways in the regulation of growth hormone release by somatostatin and growth hormone-releasing hormone in orange-spotted grouper (Epinephelus coioides).
Mol Cell Endocrinol
Bin Wang, Chaobin Qin, Cong Zhang +3 more
Somatostatin is the most effective inhibitor of GH release, and GHRH was recently identified as one of the primary GH-releasing factors in teleosts. In this study, we analyzed the possible intracellular transduction pathways that are involved in the mechanisms induced by SRIF and GHRH to regulate GH release. Using a pharmacological approach, the blockade of the PLC/IP/PKC pathway reversed the SRIF-induced inhibition of GH release but did not affect the GHRH-induced stimulation of GH release. Furthermore, SRIF reduced the GH release induced by two PKC activators. Inhibitors of the AC/cAMP/PKA pathway reversed both the SRIF- and GHRH-induced effects on GH release. Moreover, the GH release evoked by forskolin and 8-Br-cAMP were completely abolished by SRIF. The blockade of the NOS/NO pathway attenuated the GHRH-induced GH release but had minimal effects on the inhibitory actions of SRIF. In addition, inhibitors of the sGC/cGMP pathway did not modify the SRIF- or GHRH-induced regulation of GH release. Taken together, these findings indicate that the SRIF-induced inhibition of GH release is mediated by both the PLC/IP/PKC and the AC/cAMP/PKA pathways and not by the NOS/NO/sGC/cGMP pathway. In contrast, the GHRH-induced stimulation of GH secretion is mediated by both the AC/cAMP/PKA and the NOS/NO pathways and is independent of the sGC/cGMP pathway and the PLC/IP/PKC system.
Sex differences in the neural and behavioral response to intranasal oxytocin and vasopressin during human social interaction.
Psychoneuroendocrinology
James K Rilling, Ashley C DeMarco, Patrick D Hackett +8 more
Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of certain psychiatric disorders that involve social behavioral deficits. In particular, there is growing interest in intranasal OT as a potential treatment for certain psychiatric disorders, and preliminary pre-clinical and clinical studies suggest efficacy in alleviating some of the associated symptoms. However, the vast majority of research participants in these studies have been male, and there is evidence for sexually differentiated effects of nonapeptides in both humans and non-human animals. To date, no study has investigated the effect of intranasal OT on brain function in human males and females within the same paradigm. Previously, in a randomized, placebo-controlled, double-blind fMRI study, we reported effects of intranasal OT and AVP on behavior and brain activity of human males as they played an interactive social game known as the Prisoner's Dilemma Game. Here, we present findings from an identical study in human females, and compare these with our findings from males. Overall, we find that both behavioral and neural responses to intranasal OT and AVP are highly sexually differentiated. In women, AVP increased conciliatory behavior, and both OT and AVP caused women to treat computer partners more like humans. In men, AVP increased reciprocation of cooperation from both human and computer partners. However, no specific drug effects on behavior were shared between men and women. During cooperative interactions, both OT and AVP increased brain activity in men within areas rich in OT and AVP receptors and in areas playing a key role in reward, social bonding, arousal and memory (e.g., the striatum, basal forebrain, insula, amygdala and hippocampus), whereas OT and AVP either had no effect or in some cases actually decreased brain activity in these regions in women. OT treatment rendered neural responses of males more similar to responses of females in the placebo group and vice versa, raising the prospect of an inverted u-shaped dose response to central OT levels. These findings emphasize the need to fully characterize the effects of intranasal OT and AVP in both males and females and at multiple doses before widespread clinical application will be warranted.
The effect of strength training volume on satellite cells, myogenic regulatory factors, and growth factors.
Scand J Med Sci Sports
K E Hanssen, N H Kvamme, T S Nilsen +7 more
The aim of this work was to study the effect of training volume on activation of satellite cells. Healthy untrained men were randomly assigned into two groups. The 3L-1UB group (n = 10) performed three-set leg exercises and single-set upper body exercises, and the 1L-3UB group (n = 11) performed single-set leg exercises and three-set upper body exercises. Both groups performed three sessions (80-90 min) per week for 11 weeks. Biopsies were taken from m. vastus lateralis and m. trapezius. The number of satellite cells, satellite cells positive for myogenin and MyoD, and the number of myonuclei were counted. Homogenized muscle was analyzed for myogenin and MyoD, and extracted ribonucleic acid (RNA) was monitored for selected growth factor transcripts. Knee extensor strength increased more in the 3L-1UB group than in the 1L-3UB group (48 ± 4% vs 29 ± 4%), whereas the strength gain in shoulder press was similar in both training groups. The number of satellite cells in m. vastus lateralis increased more in the 3L-1UB group than in the 1L-3UB group. The number of myonuclei increased similarly in both groups. The messenger RNA expression of growth factors peaked after 2 weeks of training. In conclusion, increasing training volume enhanced satellite cell numbers in the leg muscle, but not in the upper body muscle.
Neuropeptides in learning and memory.
Neuropeptides
Eva Borbély, Bálint Scheich, Zsuzsanna Helyes
Dementia conditions and memory deficits of different origins (vascular, metabolic and primary neurodegenerative such as Alzheimer's and Parkinson's diseases) are getting more common and greater clinical problems recently in the aging population. Since the presently available cognitive enhancers have very limited therapeutical applications, there is an emerging need to elucidate the complex pathophysiological mechanisms, identify key mediators and novel targets for future drug development. Neuropeptides are widely distributed in brain regions responsible for learning and memory processes with special emphasis on the hippocampus, amygdala and the basal forebrain. They form networks with each other, and also have complex interactions with the cholinergic, glutamatergic, dopaminergic and GABA-ergic pathways. This review summarizes the extensive experimental data in the well-established rat and mouse models, as well as the few clinical results regarding the expression and the roles of the tachykinin system, somatostatin and the closely related cortistatin, vasoactive intestinal polypeptide (VIP) and pituitary adenylate-cyclase activating polypeptide (PACAP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), opioid peptides and galanin. Furthermore, the main receptorial targets, mechanisms and interactions are described in order to highlight the possible therapeutical potentials. Agents not only symptomatically improving the functional impairments, but also inhibiting the progression of the neurodegenerative processes would be breakthroughs in this area. The most promising mechanisms determined at the level of exploratory investigations in animal models of cognitive disfunctions are somatostatin sst4, NPY Y2, PACAP-VIP VPAC1, tachykinin NK3 and galanin GALR2 receptor agonisms, as well as delta opioid receptor antagonism. Potent and selective non-peptide ligands with good CNS penetration are needed for further characterization of these molecular pathways to complete the preclinical studies and decide if any of the above described targets could be appropriate for clinical investigations.
Blood flow restricted resistance training attenuates myostatin gene expression in a patient with inclusion body myositis.
Biol Sport
A R Santos, M T Neves, B Gualano +5 more
Inclusion body myositis is a rare idiopathic inflammatory myopathy that produces extreme muscle weakness. Blood flow restricted resistance training has been shown to improve muscle strength and muscle hypertrophy in inclusion body myositis.
[Effect of deltaran and melatonin on immune system in rats with experimental contact dermatitis].
Fiziol Zh (1994)
O O Shandra
The aim of the work was investigation of both humoral and cell-mediated immunity together with leukocytes functional stability indexes in rats with the experimental contact dermatitis (ECD) in conditions of complex pharmacological correction using deltaran and melatonin. Experimental trials were performed under conditions of chronic experiment on model chrome-induced ECD. Both deltaran and melatonin either alone or in combination were used for complex pharmacological correction of humoral and cell-mediated immunity and also for stability of leukocytes. The data obtained showed the expressed disturbances of humoral and cell-mediated immunity and neutrophils' functional stability damage under conditions of chrome-induced ECD in rats. The revealed alterations in functional activity of the immune system were successfully corrected using the combined administration of deltaran and melatonin. The activity of medical complex had exponential character.
[Neuroprotective effects of peptides bioregulators in people of various age].
Adv Gerontol
R S Umnov, N S Lin'kova, V Kh Khavinson
The review presents comparative characteristics of 2 peptide neuroprotective groups: polypeptide complexes (cortexin, cerebrolizin) and short peptides (semax, kortagen, pinealon). The data of clinical applying of peptides in elderly and old age people and cellular and molecular mechanisms of their neuroprotective activity is described.
The role of oxytocin in plasticity, memory and attachment dynamics.
J Biol Regul Homeost Agents
F Orsucci, G Paoloni, C M Conti +2 more
The peptide hormones oxytocin (OT) and arginine vasopressin (AVP) have been implicated in the regulation of mammalian social behavior. There is considerable evidence implicating both oxytocin and vasopressin in social recognition and social memory. This review explores their role in attachment dynamics. Oxytocin is one element in a complex network of interactions observed in natural phenomena ranging from molecular biology, etology, social behavior and human psychology.
[Protective effect of selank on the model of mnestic function violation induced by pharmacological blockade of protein synthesis].
Eksp Klin Farmakol
I I Kozlovskiĭ, F Iu Belozertsev, L A Andreeva +1 more
We have studied the ability of peptide anxiolytic selank (Thr-Lyz-Pro-Arg-Pro-Gly-Pro) to compensate for mnestic dysfunction caused by the administration of actinomycin D, which inhibits protein synthesis by blocking DNA-dependent RNA polymerase. The experiments were performed on white rats with acquired adaptive ability of spatial visual orientation in a 16-door labyrinth. The learning was based on the avoidance of electric skin irritation at alternating sites of escape reaction (site reflex). Selank (0.5 mg/kg, i.p.) prevented or compensated for actinomycin D (250 mg/kg, i.p.) induced violation of the process of acquisition, improvement, and consolidation of memory trace during the development of a complex site reflex. The drug administration also reduced the time required for acquisition of the adaptive ability of spatial visual orientation in the labyrinth and restored the actinomycin D violated process of re-learning upon a change in the alternation of escape sites under free-choice conditions.
The effects of 11-ketotestosterone on ovarian physiology of previtellogenic captive hapuku (Polyprion oxygeneios).
Comp Biochem Physiol A Mol Integr Physiol
Yair Y Kohn, Jane E Symonds, P Mark Lokman
The present study investigated, for the first time in a perciform teleost, the effects of in vivo 11-ketotestosterone (11-KT) treatment using slow-release implants on ovarian development and gonadotropin receptor mRNA levels in captive previtellogenic females of hapuku (Polyprion oxygeneios). At the cellular/functional level, ovarian development and ovarian and hepatic total lipid levels were examined. At the molecular level, transcript abundance of ovarian follicle-stimulating hormone receptor (FSH-R) and luteinizing hormone receptor (LH-R) was measured. Additionally, cyclic adenosine monophosphate (cAMP) levels in ovarian fragments from placebo and 11-KT implanted fish incubated with or without human chorionic gonadotropin (hCG) in vitro were compared between groups. There were no significant differences between treatments with regard to oocyte size and lipid contents of liver and ovary. Messenger RNA levels of FSH-R and LH-R were significantly lower in the treated females. Similarly, cAMP levels were significantly lower in the ovarian fragments of the 11-KT implanted females. These results suggest that 11-KT specifically, but possibly androgens in general, may not have an important function in regulating gonadal development of previtellogenic female hapuku; indeed, if anything, 11-KT appeared to have a detrimental effect and its use will not be beneficial in advancing sexual maturity of hapuku in aquaculture.
Heart failure-induced skeletal myopathy in spontaneously hypertensive rats.
Int J Cardiol
R L Damatto, P F Martinez, A R R Lima +10 more
Although skeletal muscle atrophy and changes in myosin heavy chain (MyHC) isoforms have often been observed during heart failure, their pathophysiological mechanisms are not completely defined. In this study we tested the hypothesis that skeletal muscle phenotype changes are related to myogenic regulatory factors and myostatin/follistatin expression in spontaneously hypertensive rats (SHR) with heart failure.
Synthesis and characterization of time-resolved fluorescence probes for evaluation of competitive binding to melanocortin receptors.
Bioorg Med Chem
Ramesh Alleti, Josef Vagner, Dilani Chathurika Dehigaspitiya +10 more
Probes for use in time-resolved fluorescence competitive binding assays at melanocortin receptors based on the parental ligands MSH(4), MSH(7), and NDP-α-MSH were prepared by solid phase synthesis methods, purified, and characterized. The saturation binding of these probes was studied using HEK-293 cells engineered to overexpress the human melanocortin 4 receptor (hMC4R) as well as the human cholecystokinin 2 receptor (hCCK2R). The ratios of non-specific binding to total binding approached unity at high concentrations for each probe. At low probe concentrations, receptor-mediated binding and uptake was discernable, and so probe concentrations were kept as low as possible in determining Kd values. The Eu-DTPA-PEGO-MSH(4) probe exhibited low specific binding relative to non-specific binding, even at low nanomolar concentrations, and was deemed unsuitable for use in competition binding assays. The Eu-DTPA-PEGO probes based on MSH(7) and NDP-α-MSH exhibited Kd values of 27±3.9nM and 4.2±0.48nM, respectively, for binding with hMC4R. These probes were employed in competitive binding assays to characterize the interactions of hMC4R with monovalent and divalent MSH(4), MSH(7), and NDP-α-MSH constructs derived from squalene. Results from assays with both probes reflected only statistical enhancements, suggesting improper ligand spacing on the squalene scaffold for the divalent constructs. The Ki values from competitive binding assays that employed the MSH(7)-based probe were generally lower than the Ki values obtained when the probe based on NDP-α-MSH was employed, which is consistent with the greater potency of the latter probe. The probe based on MSH(7) was also competed with monovalent, divalent, and trivalent MSH(4) constructs that previously demonstrated multivalent binding in competitive binding assays against a variant of the probe based on NDP-α-MSH. Results from these assays confirm multivalent binding, but suggest a more modest increase in avidity for these MSH(4) constructs than was previously reported.
Mechano-growth factor peptide, the COOH terminus of unprocessed insulin-like growth factor 1, has no apparent effect on myoblasts or primary muscle stem cells.
Am J Physiol Endocrinol Metab
Mara Fornaro, Aaron C Hinken, Saul Needle +12 more
A splice form of IGF-1, IGF-1Eb, is upregulated after exercise or injury. Physiological responses have been ascribed to the 24-amino acid COOH-terminal peptide that is cleaved from the NH3-terminal 70-amino acid mature IGF-1 protein. This COOH-terminal peptide was termed "mechano-growth factor" (MGF). Activities claimed for the MGF peptide included enhancing muscle satellite cell proliferation and delaying myoblast fusion. As such, MGF could represent a promising strategy to improve muscle regeneration. Thus, at our two pharmaceutical companies, we attempted to reproduce the claimed effect of MGF peptides on human and mouse muscle myoblast proliferation and differentiation in vitro. Concentrations of peptide up to 500 ng/ml failed to increase the proliferation of C2C12 cells or primary human skeletal muscle myoblasts. In contrast, all cell types exhibited a proliferative response to mature IGF-1 or full-length IGF-1Eb. MGF also failed to inhibit the differentiation of myoblasts into myotubes. To address whether the response to MGF was lost in these tissue culture lines, we measured proliferation and differentiation of primary mouse skeletal muscle stem cells exposed to MGF. This, too, failed to demonstrate a significant effect. Finally, we tested whether MGF could alter a separate documented in vitro effect of the peptide, activation of p-ERK, but not p-Akt, in cardiac myocytes. Although a robust response to IGF-1 was observed, there were no demonstrated activating responses from the native or a stabilized MGF peptide. These results call in to question whether there is a physiological role for MGF.
[Metabolic effects of delta-sleep inducing peptide during physiological aging of the organism].
Eksp Klin Farmakol
T I Bondarenko, E A Maĭboroda, I I Mikhaleva +1 more
Subcutaneous injection of delta-sleep inducing peptide (DSIP) to postnatal rats (aged from 2 to 24 months) during 5 consecutive days every months at a dose of 10 microg/100 g body weight favors normalization of the age-related changes in carbohydrate metabolism and shows hypoglycemic effect, as manifested by a decrease in the level of glycosylated hemoglobin in erythrocytes of test rats. The administration of DSIP in postnatal rats of different age also led to a decrease in serum total lipid level, total cholesterol level, and atherogenicity index and an increase in the level of high-density lipoprotein cholesterol.
Single administration of tripeptide α-MSH(11-13) attenuates brain damage by reduced inflammation and apoptosis after experimental traumatic brain injury in mice.
PLoS One
Eva-Verena Schaible, Arne Steinsträßer, Antje Jahn-Eimermacher +7 more
Following traumatic brain injury (TBI) neuroinflammatory processes promote neuronal cell loss. Alpha-melanocyte-stimulating hormone (α-MSH) is a neuropeptide with immunomodulatory properties, which may offer neuroprotection. Due to short half-life and pigmentary side-effects of α-MSH, the C-terminal tripeptide α-MSH(11-13) may be an anti-inflammatory alternative. The present study investigated the mRNA concentrations of the precursor hormone proopiomelanocortin (POMC) and of melanocortin receptors 1 and 4 (MC1R/MC4R) in naive mice and 15 min, 6, 12, 24, and 48 h after controlled cortical impact (CCI). Regulation of POMC and MC4R expression did not change after trauma, while MC1R levels increased over time with a 3-fold maximum at 12 h compared to naive brain tissue. The effect of α-MSH(11-13) on secondary lesion volume determined in cresyl violet stained sections (intraperitoneal injection 30 min after insult of 1 mg/kg α-MSH(11-13) or 0.9% NaCl) showed a considerable smaller trauma in α-MSH(11-13) injected mice. The expression of the inflammatory markers TNF-α and IL-1β as well as the total amount of Iba-1 positive cells were not reduced. However, cell branch counting of Iba-1 positive cells revealed a reduced activation of microglia. Furthermore, tripeptide injection reduced neuronal apoptosis analyzed by cleaved caspase-3 and NeuN staining. Based on the results single α-MSH(11-13) administration offers a promising neuroprotective property by modulation of inflammation and prevention of apoptosis after traumatic brain injury.
Ageing is associated with diminished muscle re-growth and myogenic precursor cell expansion early after immobility-induced atrophy in human skeletal muscle.
J Physiol
C Suetta, U Frandsen, A L Mackey +9 more
Recovery of skeletal muscle mass from immobilisation-induced atrophy is faster in young than older individuals, yet the cellular mechanisms remain unknown. We examined the cellular and molecular regulation of muscle recovery in young and older human subjects subsequent to 2 weeks of immobility-induced muscle atrophy. Retraining consisted of 4 weeks of supervised resistive exercise in 9 older (OM: mean age) 67.3, range 61-74 yrs) and 11 young (YM: mean age 24.4, range 21-30 yrs) males. Measures of myofibre area (MFA), Pax7-positive satellite cells (SCs) associated with type I and type II muscle fibres, as well as gene expression analysis of key growth and transcription factors associated with local skeletal muscle milieu, were performed after 2 weeks immobility (Imm) and following 3 days (+3d) and 4 weeks (+4wks) of retraining. OM demonstrated no detectable gains in MFA (vastus lateralis muscle) and no increases in number of Pax7-positive SCs following 4wks retraining, whereas YM increased their MFA (P < 0.05), number of Pax7-positive cells, and had more Pax7-positive cells per type II fibre than OM at +3d and +4wks (P < 0.05). No age-related differences were observed in mRNA expression of IGF-1Ea, MGF, MyoD1 and HGF with retraining, whereas myostatin expression levels were more down-regulated in YM compared to OM at +3d (P < 0.05). In conclusion, the diminished muscle re-growth after immobilisation in elderly humans was associated with a lesser response in satellite cell proliferation in combination with an age-specific regulation of myostatin. In contrast, expression of local growth factors did not seem to explain the age-related difference in muscle mass recovery.
[Olygopeptide KND as a putative endogenous prototype of delta sleep inducing peptide (DSIP). Comparative study of biological properties].
Bioorg Khim
I I Mikhaleva, V T Ivanov, V B Voĭtenkov +2 more
We have undertaken a comparative study on physiological activity of well known neuropeptide DSIP (WAGGDASG E) and new closely related peptide KND (WKGGNASGE) in vivo assays. The sequence of K2, N5-DSIP (KND) was found recently by the computer search for DSIP homologous sequences in available nucleotide and protein databases at 324-332 site of Lysine-specific demethylase 3 B (EC 1.14.11, Swiss-Prot: Q7LBC6.1, 1-1761aa). This human lysine-specific histone demethylase is a representative of the recently discovered family of so called JmjC-domain-containing histone demethylases encoded by JMJD1B gene and ubiquitously expressed in tissues of various mammalian species. Biological investigations performed in this work confirm our preliminary data that DSIP-related peptide KND exhibits the similar biological properties in comparison with DSIP. Assessed by us antioxidative, anticonvulsive and behavioral effects of KND were even more expressed than in DSIP case. These results provide the additional evidences to support our suggestion that KND can be a possible endogenous prototype of "real" DSIP.