Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study focuses on presympathetic neurons of the rostral ventrolateral medulla (RVLM) that regulate sympathetic vasomotor tone. Many neurotransmitters are colocalized in RVLM neurons and are released under specific conditions to modulate efferent homeostatic responses. Of particular interest here are two peptides colocalized in catecholaminergic RVLM neurons: catestatin and pituitary adenylate cyclase-activating polypeptide (PACAP). Chromogranin A-derived catestatin is a potent endogenous noncompetitive nicotinic and adrenoreceptor antagonist. Catestatin impairs adenylate cyclase and phospholipase C action: mechanisms engaged by PACAP. Although PACAP and catestatin are likely coreleased, the possible effects of this are unknown. We aimed to determine whether catestatin affects the normal sympathoexcitatory but isotensive responses to intrathecal PACAP. Urethane-anesthetized, vagotomized, ventilated Sprague-Dawley rats (n = 22) were given an intrathecal injection of catestatin at different times prior to intrathecal administration of PACAP-38. Arterial pressure, splanchnic sympathetic nerve activity, heart rate, and reflex responses to baroreceptor and chemoreceptor activation were recorded. The key findings of this study are that pretreatment with catestatin time dependently enhances the PACAP-38 effect on mean arterial pressure and enhances sympathetic barosensitivity and chemosensitivity. The time-scale of the effect of catestatin on the response to PACAP-38 strongly suggests that catestatin is either causing changes in gene expression to exert its effects, or modifying intracellular mechanisms normally engaged by PAC(1) receptors. The ability of catestatin pretreatment to enhance barosensitivity and chemosensitivity after PACAP-38 injection supports the hypothesis that catestatin manipulates the intracellular environment within sympathetic neurons in a way that increases responses to PACAP.
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PMID:Catestatin has an unexpected effect on the intrathecal actions of PACAP dramatically reducing blood pressure. 2287 27

VIP and PACAP are pleiotropic peptides belonging to the secretin superfamily of brain-gut peptides and interact specifically with three receptors (VPAC(1), PAC(1) and VPAC(2)) from the class II B G protein-coupled receptor family. There is immense interest regarding their molecular evolution which is often described closely alongside gene and/or genome duplications. Despite the wide array of information available in various vertebrates and one invertebrate the tunicate, their evolutionary origins remain unresolved. Through searches of genome databases and molecular cloning techniques, the first lamprey VIP/PACAP ligands and VPAC receptors are identified from the Japanese lamprey. In addition, two VPAC receptors (VPACa/b) are identified from inshore hagfish and ligands predicted for sea lamprey. Phylogenetic analyses group these molecules into their respective PHI/VIP, PRP/PACAP and VPAC receptor families and show they resemble ancestral forms. Japanese lamprey VIP/PACAP peptides synthesized were tested with the hagfish VPAC receptors. hfVPACa transduces signal via both adenylyl cylase and phospholipase C pathways, whilst hfVPACb was only able to transduce through the calcium pathway. In contrast to the widespread distribution of VIP/PACAP ligands and receptors in many species, the agnathan PACAP and VPAC receptors were found almost exclusively in the brain. In situ hybridisation further showed their abundance throughout the brain. The range of VIP/PACAP ligands and receptors found are highly useful, providing a glimpse into the evolutionary events both at the structural and functional levels. Though representative of ancestral forms, the VIP/PACAP ligands in particular have retained high sequence conservation indicating the importance of their functions even early in vertebrate evolution. During these nascent stages, only two VPAC receptors are likely responsible for eliciting functions before evolving later into specific subtypes post-Agnatha. We also propose VIP and PACAP's first functions to predominate in the brain, evolving alongside the central nervous system, subsequently establishing peripheral functions.
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PMID:Agnathan VIP, PACAP and their receptors: ancestral origins of today's highly diversified forms. 2295

Resistance to anoikis, a cell-detachment induced apoptosis, is one of the malignant phenotypes which support tumor metastasis. Molecular mechanisms underlying the establishment of this phenotype require further investigation. This study aimed at exploring protein expression profiles associated with anoikis resistance of a metastatic breast cancer cell. Cell survival of suspension cultures of non-metastatic MCF-7 and metastatic MDA-MB-231 cells were compared with their adherent cultures. Trypan blue exclusion assays demonstrated a significantly higher percentage of viable cells in MDA-MB-231 than MCF-7 cell cultures, consistent with analysis of annexin V-7-AAD stained cells indicating that MDA-MB-231 possess anti-apoptotic ability 1.7 fold higher than MCF-7 cells. GeLC-MS/MS analysis of protein lysates of MDA-MB-231 and MCF-7 cells grown under both culture conditions identified 925 proteins which are differentially expressed, 54 of which were expressed only in suspended and adherent MDA-MB-231 but not in MCF-7 cells. These proteins have been implicated in various cellular processes, including DNA replication and repair, transcription, translation, protein modification, cytoskeleton, transport and cell signaling. Analysis based on the STITCH database predicted the interaction of phospholipases, PLC and PLD, and 14-3-3 beta/alpha, YWHAB, with the intrinsic and extrinsic apoptotic signaling network, suggesting putative roles in controlling anti-anoikis ability. MDA-MB-231 cells grown in the presence of inhibitors of phospholipase C, U73122, and phospholipase D, FIPI, demonstrated reduced ability to survive in suspension culture, indicating functional roles of PLC and PLD in the process of anti-anoikis. Our study identified intracellular mediators potentially associated with establishment of anoikis resistance of metastatic cells. These proteins require further clarification as prognostic and therapeutic targets for advanced breast cancer.
Asian Pac J Cancer Prev 2016
PMID:Protein Profiles Associated with Anoikis Resistance of Metastatic MDA-MB-231 Breast Cancer Cells. 2692 47


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