Dataset Information

Curcuma amarissima Extract Activates Growth and Survival Signal Transduction Networks to Stimulate Proliferation of Human Keratinocyte.

ABSTRACT: Many medicinal plants have been used to treat wounds. Here, we revealed the potential wound healing effects of Curcuma amarissima (CA). Our cell viability assay showed that CA extract increased the viability of HaCaT cells that were cultured in the absence of serum. This increase in cell viability was proved to be associated with the pharmacological activities of CA extract in inducing cell proliferation. To further define possible molecular mechanisms of action, we performed Western blot analysis and immunofluorescence study, and our data demonstrated that CA extract rapidly induced ERK1/2 and Akt activation. Consistently, CA extract accelerated cell migration, resulting in rapid healing of wounded human keratinocyte monolayer. Specifically, the CA-induced increase of cell monolayer wound healing was blocked by the MEK inhibitor (U0126) or the PI3K inhibitor (LY294002). Moreover, CA extract induced the expression of Mcl-1, which is an anti-apoptotic protein, supporting that CA extract enhances human keratinocyte survival. Taken together, our study provided convincing evidence that Curcuma amarissima can promote proliferation and survival of human keratinocyte through stimulating the MAPK and PI3K/Akt signaling cascades. These promising data emphasize the possibility to develop this plant as a wound healing agent for the potential application in regenerative medicine.

SUBMITTER: Nimlamool W

PROVIDER: S-EPMC8067174 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

<i>Curcuma amarissima</i> Extract Activates Growth and Survival Signal Transduction Networks to Stimulate Proliferation of Human Keratinocyte.

Nimlamool Wutigri W Potikanond Saranyapin S Ruttanapattanakul Jirapak J Wikan Nitwara N Okonogi Siriporn S Jantrapirom Salinee S Pitchakarn Pornsiri P Karinchai Jirarat J

Biology 20210401 4

Many medicinal plants have been used to treat wounds. Here, we revealed the potential wound healing effects of <i>Curcuma amarissima</i> (CA). Our cell viability assay showed that CA extract increased the viability of HaCaT cells that were cultured in the absence of serum. This increase in cell viability was proved to be associated with the pharmacological activities of CA extract in inducing cell proliferation. To further define possible molecular mechanisms of action, we performed Western blot ...[more]

PMID: 33916174

Similar Datasets

Project description:Schizophrenia is a serious neuropsychiatric disorder characterized by disruptions of brain cell metabolism, microstructure, and neurotransmission. All of these processes require coordination of multiple kinase-mediated signaling events. We hypothesize that imbalances in kinase activity propagate through an interconnected network of intracellular signaling with potential to simultaneously contribute to many or all of the observed deficits in schizophrenia. We established a workflow distinguishing schizophrenia-altered kinases in anterior cingulate cortex using a previously published kinome array data set. We compared schizophrenia-altered kinases to haloperidol-altered kinases, and identified systems, functions, and regulators predicted using pathway analyses. We used kinase inhibitors with the kinome array to test hypotheses about imbalance in signaling and conducted preliminary studies of kinase proteins, phosphoproteins, and activity for kinases of interest. We investigated schizophrenia-associated single nucleotide polymorphisms in one of these kinases, AKT, for genotype-dependent changes in AKT protein or activity. Kinome analyses identified new kinases as well as some previously implicated in schizophrenia. These results were not explained by chronic antipsychotic treatment. Kinases identified in our analyses aligned with cytoskeletal arrangement and molecular trafficking. Of the kinases we investigated further, AKT and (unexpectedly) JNK, showed the most dysregulation in the anterior cingulate cortex of schizophrenia subjects. Changes in kinase activity did not correspond to protein or phosphoprotein levels. We also show that AKT single nucleotide polymorphism rs1130214, previously associated with schizophrenia, influenced enzyme activity but not protein or phosphoprotein levels. Our data indicate subtle changes in kinase activity and regulation across an interlinked kinase network, suggesting signaling imbalances underlie the core symptoms of schizophrenia. DISEASE MECHANISMS:A SIGNALING IMBALANCE: A study by US scientists indicates that changes in the activity of key signaling proteins may underlie core symptoms of schizophrenia. Protein kinases mediate the activation of intracellular signaling events and analyses of the kinome, the complete set of protein kinases encoded in the genome, previously revealed significant changes in phosphorylation patterns in postmortem brain tissue from patients with schizophrenia. Based on these findings, Jennifer McGuire at the University of Cincinnati and colleagues investigated the upstream regulation of these proteins. They identified both established and novel proteins associated with schizophrenia in the anterior cingulate cortex, with JNK and AKT activity being the most disrupted in schizophrenia patients. Their findings highlight how subtle changes in the activity of a small number of signaling proteins can propagate and have major consequences for mental health.

Project description:BACKGROUND: Spatial signal transduction plays a vital role in many intracellular processes such as eukaryotic chemotaxis, polarity generation and cell division. Furthermore it is being increasingly realized that the spatial dimension to signalling may play an important role in other apparently purely temporal signal transduction processes. It is increasingly being recognized that a conceptual basis for studying spatial signal transduction in signalling networks is necessary. RESULTS: In this work we examine spatial signal transduction in a series of standard motifs/networks. These networks include coherent and incoherent feedforward, positive and negative feedback, cyclic motifs, monostable switches, bistable switches and negative feedback oscillators. In all these cases, the driving signal has spatial variation. For each network we consider two cases, one where all elements are essentially non-diffusible, and the other where one of the network elements may be highly diffusible. A careful analysis of steady state signal transduction provides many insights into the behaviour of all these modules. While in the non-diffusible case for the most part, spatial signalling reflects the temporal signalling behaviour, in the diffusible cases, we see significant differences between spatial and temporal signalling characteristics. Our results demonstrate that the presence of diffusible elements in the networks provides important constraints and capabilities for signalling. CONCLUSIONS: Our results provide a systematic basis for understanding spatial signalling in networks and the role of diffusible elements therein. This provides many insights into the signal transduction capabilities and constraints in such networks and suggests ways in which cellular signalling and information processing is organized to conform to or bypass those constraints. It also provides a framework for starting to understand the organization and regulation of spatial signal transduction in individual processes.

Project description:Networks of fixed topology are used to summarize the collective understanding of the flow of signaling information within a cell (i.e., canonical signaling networks). Moreover, these canonical signaling networks are used to interpret how observed oncogenic changes in protein activity or expression alter information flow in cancer cells. However, creating a novel branch within a signaling network (i.e., a noncanonical edge) provides a mechanism for a cell to acquire the hallmark characteristics of cancer. The objective of this study was to assess the existence of a noncanonical edge within a receptor tyrosine kinase (RTK) signaling network based upon variation in protein expression alone, using a mathematical model of the early signaling events associated with epidermal growth factor receptor 1 (ErbB1) signaling network as an illustrative example. The abundance of canonical protein-RTK complexes (e.g., growth factor receptor bound protein 2-ErbB1 and Src homology 2 domain containing transforming protein 1-ErbB1) were used to establish a threshold that was correlated with ligand-dependent changes in cell proliferation. Given the available data, the uncertainty associated with this threshold was estimated using an empirical Bayesian approach. Using the variability in protein expression observed among a collection of breast cancer cell lines, this model was used to assess whether a noncanonical edge (e.g., Irs1-ErbB1) exceeds the threshold and to identify cell lines where this noncanonical edge is likely to be observed. Taken together, the simulations suggest that the topology of signal transduction networks within cells is influenced by quantitative parameters, such as protein expression and binding affinity. Moreover, forming this noncanonical pathway was not due solely to overexpression of the cell surface receptor but was influenced by overexpression of all members of the multiprotein complex. Multivariate alterations in expression of signaling proteins in cancer cells may activate noncanonical pathways and may rewire the signaling network within a cell.

Dataset Information

Curcuma amarissima Extract Activates Growth and Survival Signal Transduction Networks to Stimulate Proliferation of Human Keratinocyte.

Publications

<i>Curcuma amarissima</i> Extract Activates Growth and Survival Signal Transduction Networks to Stimulate Proliferation of Human Keratinocyte.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets