Nucleotides as Bacterial Second Messengers.

In addition to comprising monomers of nucleic acids, nucleotides have signaling functions and act as second messengers in both prokaryotic and eukaryotic cells. The most common example is cyclic AMP (cAMP). Nucleotide signaling is a focus of great interest in bacteria. Cyclic di-AMP (c-di-AMP), cAMP, and cyclic di-GMP (c-di-GMP) participate in biological events such as bacterial growth, biofilm formation, sporulation, cell differentiation, motility, and virulence. Moreover, the cyclic-di-nucleotides (c-di-nucleotides) produced in pathogenic intracellular bacteria can affect eukaryotic host cells to allow for infection. On the other hand, non-cyclic nucleotide molecules pppGpp and ppGpp are alarmones involved in regulating the bacterial response to nutritional stress; they are also considered second messengers. These second messengers can potentially be used as therapeutic agents because of their immunological functions on eukaryotic cells. In this review, the role of c-di-nucleotides and cAMP as second messengers in different bacterial processes is addressed.

Modulating cyclic nucleotides pathways by bioactive compounds in combatting anxiety and depression disorders.

Anxiety and depression disorders are highly prevalent neurological disorders (NDs) that impact up to one in three individuals during their lifetime. Addressing these disorders requires reducing their frequency and impact, understanding molecular causes, implementing prevention strategies, and improving treatments. Cyclic nucleotide monophosphates (cNMPs) like cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cyclic uridine monophosphate (cUMP), and cyclic cytidine monophosphate (cCMP) regulate the transcription of genes involved in neurotransmitters and neurological functions. Evidence suggests that cNMP pathways, including cAMP/cGMP, cAMP response element binding protein (CREB), and Protein kinase A (PKA), play a role in the physiopathology of anxiety and depression disorders. Plant and mushroom-based compounds have been used in traditional and modern medicine due to their beneficial properties. Bioactive compound metabolism can activate key pathways and yield pharmacological outcomes. This review focuses on the molecular mechanisms of bioactive compounds from plants and mushrooms in modulating cNMP pathways. Understanding these processes will support current treatments and aid in the development of novel approaches to reduce the prevalence of anxiety and depression disorders, contributing to improved outcomes and the prevention of associated complications.

A novel light-dependent activation of DAGK and PKC in bovine photoreceptor nuclei.

In this work, we describe a selective light-dependent distribution of the lipid kinase 1,2-diacylglycerol kinase (EC 2.7.1.107, DAGK) and the phosphorylated protein kinase C alpha (pPKCα) in a nuclear fraction of photoreceptor cells from bovine retinas. A nuclear fraction enriched in small nuclei from photoreceptor cells (PNF), was obtained when a modified nuclear isolation protocol developed by our laboratory was used. We measured and compared DAGK activity as phosphatidic acid (PA) formation in PNF obtained from retinas exposed to light and in retinas kept in darkness using [γ-(32)P]ATP or [(3)H]DAG. In the absence of exogenous substrates and detergents, no changes in DAGK activity were observed. However, when DAGK activity assays were performed in the presence of exogenous substrates, such as stearoyl arachidonoyl glycerol (SAG) or dioleoyl glycerol (DOG), and different detergents (used to make different DAGK isoforms evident), we observed significant light effects on DAGK activity, suggesting the presence of several DAGK isoforms in PNF. Under conditions favoring DAGKζ activity (DOG, Triton X-100, dioleoyl phosphatidylserine and R59022) we observed an increase in PA formation in PNF from retinas exposed to light with respect to those exposed to darkness. In contrast, under conditions favoring DAGKɛ (SAG, octylglucoside and R59022) we observed a decrease in its activity. These results suggest different physiological roles of the above-mentioned DAGK isoforms. Western blot analysis showed that whereas light stimulation of bovine retinas increases DAGKζ nuclear content, it decreases DAGKɛ and DAGKß content in PNF. The role of PIP2-phospholipase C in light-stimulated DAGK activity was demonstrated using U73122. Light was also observed to induce enhanced pPKCα content in PNF. The selective distribution of DAGKζ and ɛ in PNF could be a light-dependent mechanism that in vertebrate retina promotes selective DAG removal and PKC regulation.

Mecanismos intrccelulares involucrados en el aprendizaje y la memoria del miedo / Intracellular mechanisms involved in the learning and memory of fear

La neurobiología del miedo consiste en una amplia configuración celular que implica la actividad en conjunto de un gran número de neuronas. Tales conexiones sufren cambios a lo largo de la vida en un proceso dependiente de la actividad celular. Esto hace variar la efectividad de la comunicación sináptica, facilitando el desencadenamiento del miedo. Por eso, esta revisión tiene como fin describir los procesos fisiológicos causantes de ese cambio celular en el miedo, los cuales inician con la activación de receptores iónicos y metabotrópicos, para finalizar con la estimulación genómica y la síntesis de proteínas. Así mismo, exponer la relación del miedo mientras se establecen memorias asociadas con él, como un factor que contribuye a una alta frecuencia de descarga y despolarización celular que favorece los cambios a largo plazo debido a la intensa excitación neuronal. Se concluye que, neurobiológicamente, el miedo puede fortalecerse luego de estimulaciones aversivas, mediante la formación de asociaciones entre estímulos y, a su vez, de éstos con el contexto, lo que le propicia al organismo una reactividad más eficiente frente a un encuentro posterior con la misma amenaza o circunstancia.

The neurobiology of fear is a large cellular configuration that implies the group activity of a large number of neurons. These connections suffer changes along the life cycle in a cellular activity-dependant process. This changes the effectiveness of the synaptic communication, facilitating the unchaining process of fear. Hence, the objective of this review is to describe the physiological process that cause those changes in fear, which begin with the activation of ionics and metabotropics receptors, and ending with the genomic stimulation and protein synthesis. Additionally, this paper explains the relation of fear while memories associated with it are established, as a factor that contributes to a higher frequency of discharging and cellular depolarization that favors long term changes due to intense neural excitation. In conclusion, fear can be neurobiologically strengthened after aversive stimulations, by the formation of associations between stimuli, as well as between them and the context, encouraging the organism to have a more efficient reactivity regarding a later meeting with the same threat or circumstance.

Segundos mensajeros / Second messengers

En esta revision se describen, de manera esquematica, los mecanismos de accion empleados por los Segundos Mensajeros comenzando por el estimulo del receptor y continuando con las reacciones en cadena que conducen finalmente a una respuesta celular.

This review schematically describes the different mechanisms of action that Second Messengers employ to stimulate receptors and then Initiate a chain of reactions that finally lead to appropriate cellular responses.