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Journal Article 2015; 36(3): 187-192 PubMed PMID: 26313381 Citation  Keywords:  Biological Clocks:physiology, Humans, Melatonin:physiology, Signal Transduction:physiology, Time,.   

: Temporal organization plays a key role in humans, and presumably all species on Earth. A core building block of the chronobiological architecture is the master clock, located in the suprachi asmatic nuclei [SCN], which organizes "when" things happen in sub-cellular biochemistry, cells, organs and organisms, including humans. Conceptually, time messenging should follow a 5 step-cascade. While abundant evidence suggests how steps 1 through 4 work, step 5 of "how is central time information transmitted througout the body?" awaits elucidation. Step 1: Light provides information on environmental (external) time; Step 2: Ocular interfaces between light and biological (internal) time are intrinsically photosensitive retinal ganglion cells [ipRGS] and rods and cones; Step 3: Via the retinohypothalamic tract external time information reaches the light-dependent master clock in the brain, viz the SCN; Step 4: The SCN translate environmental time information into biological time and distribute this information to numerous brain structures via a melanopsin-based network. Step 5: Melatonin, we propose, transmits, or is a messenger of, internal time information to all parts of the body to allow temporal organization which is orchestrated by the SCN. Key reasons why we expect melatonin to have such role include: First, melatonin, as the chemical expression of darkness, is centrally involved in time- and timing-related processes such as encoding clock and calendar information in the brain; Second, melatonin travels throughout the body without limits and is thus a ubiquitous molecule. The chemial conservation of melatonin in all tested species could make this molecule a candidate for a universal time messenger, possibly constituting a legacy of an all-embracing evolutionary history....

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Journal Article 2015; 36(1): 7-14 PubMed PMID: 25789584 Citation  Keywords:  A Kinase Anchor Proteins:physiology, Animals, Humans, Signal Transduction:physiology,.   

OBJECTIVE: Kinase Anchoring Proteins (AKAPs) have evolved to regulate the spatial and temporal organization of cellular signal transduction. As a typical member, AKAP5 which consisting of three orthologues: bovine AKAP75, rodent AKAP150 and human AKAP79, is the best known model in the anchoring and targeting properties. It is shown that AKAP5 can bind β2-adrenergic receptor, which is a member of GPCR superfamily, and orchestrate the interactions of various protein kinases, protein phosphatases and cytoskeletal element. AKAP5 is originally identified as a component of the postsynaptic density in neurons and plays a vital role in modulating neuronal activities. Subsequently, the AKAP5 complexes are also detected in other tissues and participated in various processes....

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Journal Article 2014; 35(1): 13-19 PubMed PMID: 24625911 Citation  Keywords:  Actins:chemistry, Animals, Brain-Derived Neurotrophic Factor:physiology, Female, Hippocampus:cytology, Interleukin-1beta:physiology, NF-kappa B:antagonists & inhibitors, Neurons:cytology, Rats, Rats, Wistar, Signal Transduction:physiology,.   

OBJECTIVES: To examine the effect of BDNF on F-actin during the stimulation of IL-1β in hippocampal neurons.

MATERIALS & METHODS: We cultured hippocampal neurons from rat embryos. Cell stimulation was induced by IL-1β. Cell culture success was evaluated by an activity analysis of CCK-8, staining of gliocyte by immunohistochemistry. Changes in F-actin, BDNF and NF-ĸB were examined using molecular analyses.

RESULTS: Our results demonstrate that a high concentration of IL-1β exaggerates the stimulation-induced degradation of F-actin by BDNF, whereas a low concentration of IL-1β protects F-actin against this degradation. These beneficial effects might be associated with the inhibition or exaggeration of the NF-ĸB signaling cascade.

CONCLUSIONS: Taken together, our findings indicate that BDNF acts as an F-actin-protective regulator during stimulation by IL-1β and that this function largely occurs via the regulation of NF- ĸB signaling. These results suggest that interventions targeting the BDNF signaling system may be of therapeutic value against major depressive disorder (MDD)....

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Journal Article 2011; 32(5): 607-615 PubMed PMID: 22167139 Citation  Keywords:  Animals, Humans, Neurosecretory Systems:physiology, Receptors, G-Protein-Coupled:physiology, Signal Transduction:physiology,.   

: Within the last two decades of studies in the ever-expanding field of GPCR signaling, challenging insights were adopted. Growing evidence now asists the shift from classical linear model of signaling towards a considerably complex network of signaling pathways with many shared proteins and cross-talks. Considering the extensive and intriguing network of pathways activated by these receptors, it is apparent that multi-level system of regulation must exist to rigorously modulate the amplitude, duration and spatial aspects of the GPCR signaling. This review summarizes the principal mechanisms of GPCR regulation and gives the overview of recent advances in this field of research....

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Journal Article 2011; 32(4): 563-572 PubMed PMID: 21876489 Citation  Keywords:  Female, Gastrointestinal Hormones:genetics, Gene Expression:physiology, Humans, Myometrium:physiology, Placenta:physiology, Pre-Eclampsia:etiology, Pregnancy, RNA, Messenger:metabolism, Receptors, G-Protein-Coupled:genetics, Signal Transduction:physiology.   

OBJECTIVE: Preeclampsia (PE) is a hypertensive complication of the pregnancy. In our study we investigated the expression, localization, and signaling pathways of PK1 and PKR1 in third-trimester human placenta and myometrium and assessed the correlation between the PK1 and PKR1 expression and signaling and the incidence of the PE.

MATERIALS & METHODS: We designed two study groups: pregnant PE patients and healthy, pregnant women. After collection, tissue was placed in RNAlater for RNA extraction, fixed in 4% neutral buffered formalin, and wax embedded for immunohistochemistry or placed in RPMI and transported to the laboratory for in vitro culture. We have collected and processed placental and myometrial biopsies from 40 patients - 19 were PE patients.

RESULTS: Only the PK1 mRNA expression comparison between PE and CTRL in placenta showed statistically significant difference (p=0.004). There was statistically significant difference in cell signaling in myometrium controls in 30 minutes after ligand. The rise in pERK/tERK ratio is clearly visible in time intervals 20 and 30 minutes in controls, although with no statistical significance. There was no difference in PK1 and PKR1 localization in the placenta and myometrium in the groups.

CONCLUSIONS: The number of PKR1 is not reduced in PE. The reduced PK1 mRNA expression is not than dependent on PKR1 mRNA expression. The data shows that ST produces much more PK1 in healthy pregnant women than those suffering from PE. We can conclude that in PE the production of PK1 is impaired and so are the endocrine functions of the ST....

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Clinical Trial 2005; 26(5): 493-498 PubMed PMID: 16264413 Citation  Keywords:  Adult, Circadian Rhythm:physiology, Humans, Light, Lighting, Male, Melatonin:blood, Middle Aged, Photic Stimulation, Pupil:physiology, Retina:physiology, Signal Transduction:physiology,.   

OBJECTIVES: Published data, both on nocturnal melatonin suppression in humans and on widely accepted retinal structure and function, suggest that spectral opponency plays a role in human circadian phototransduction. We directly test subadditivity, implied by spectral opponency, in human circadian phototransduction in response to nearly monochromatic and to polychromatic light.

METHODS: Adult male human subjects were exposed for 60 minutes to two intensities each of two lighting conditions, during nighttime experimental sessions. One condition consisted of light from mercury vapor lamps (450 and 1050 lx), and one condition consisted of light from these lamps filtered such that only the spectral line from this lamp at 436 nm was presented to subjects (7.5 and 15 lx).

RESULTS: Melatonin suppression from the filtered illumination at 436 nm alone was greater than mercury lamp illumination (containing energy at 436 nm in addition to other wavelengths), even when the sources exposed subjects' retinae to equal amounts of irradiance at 436 nm.

CONCLUSION: This direct test of subadditivity, together with evidence from neuroanatomy, supports the inference that spectral opponency is a fundamental characteristic of human circadian phototransduction....

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