This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term objectives of this study are to delineate the molecular mechanisms that underlie modification of cardiovascular function during stress. Stress is an important risk factor for cardiovascular diseases, but the underlying mechanisms are not well understood. The REM_SD (REMsleep deprivation) rat model of stress displays profound alterations in central autonomic pathways including cardiovascular homeostasis, feeding behavior, energy balance, and thermoregulation. Since melanocortins have been implicated in these functions, it is hypothesized that a perturbation of neural melanocortin system occurs during stress, leading to changes the responsive signal transduction pathways in central autonomic regions. Therefore, the first aim of this study to further characterize the neural melanocortin signaling system and determine the changes that occur during REM-SD stress. Antibodies will be generated against melanocortin receptors MC3-R, MC4-R and MC- 5R. The antibodies will be used to map the expression of receptor proteins in rat brain and to analyze alterations in expression patterns during REM-SD using immunoblot and immunohistochemical techniques. Proopiomelanocortin (POMC) and melanocortin receptor gene expression will also be determined by Northern blotting and RT-PCR methods. Antibodies will also be used to characterize the melanocortin signaling system by identifying the interacting partners using pull-down assays, colocalization immunohistochemistry and immunoblot analysis. Further, melanocortins are involved in many physiological processes acting both in the CNS and peripheral tissues. Literature reports indicate that in peripheral tissue cell lines, melanocortin receptors activate the cAMP, PKC and JAK/STAT signaling pathways. Neuronal signaling pathways that are modulated by melanocortins in a rodent brain stem cell line and in rats subjected to REM-SD stress will be identified using array technology and immunoblotting techniques. Those transcripts identified will be localized using in-situ hybridization and northern blotting. This study will not only provide important insights into the role and mechanism of neural melanocortin signaling system in autonomic functions, but will also identify molecular markers that play a potential role in stress related cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Centers in Minority Institutions Award (G12)
Project #
5G12RR017581-05
Application #
7336128
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2006-08-01
Project End
2007-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
5
Fiscal Year
2006
Total Cost
$104,214
Indirect Cost
Name
Morgan State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
879941318
City
Baltimore
State
MD
Country
United States
Zip Code
21251
Besold, Angelique N; Lee, Seung Jae; Michel, Sarah L J et al. (2010) Functional characterization of iron-substituted neural zinc finger factor 1: metal and DNA binding. J Biol Inorg Chem 15:583-90
Sakk, Eric; Schneider, David J; Myers, Christopher R et al. (2009) The effect of target vector selection on the invariance of classifier performance measures. IEEE Trans Neural Netw 20:745-57
Nyan, D C; Anbazhagan, R; Hughes-Darden, C A et al. (2008) Endosomal colocalization of melanocortin-3 receptor and beta-arrestins in CAD cells with altered modification of AKT/PKB. Neuropeptides 42:355-66
Benjamin 3rd, Earl; Reznik, Aron; Benjamin, Ellis et al. (2007) Mathematical models of cobalt and iron ions catalyzed microwave bacterial deactivation. Int J Environ Res Public Health 4:203-10
McMiller, Tracee L; Sims, Denise; Lee, Tameshia et al. (2007) Molecular characterization of the Caenorhabditis elegans REF-1 family member, hlh-29/hlh-28. Biochim Biophys Acta 1769:5-19
Reese, C T; Ntam, C; Martin, T V et al. (2007) Internalization of near-infrared fluorescent dyes within isolated macrophage populations. Cell Mol Biol (Noisy-le-grand) 53:27-33
Benjamin, E; Reznik, A; Benjamin, E et al. (2007) Mathematical model of manganese ion catalyzed microwave deactivation of Enterococcus faecalis, Staphylococcus aureus and Escherichia coli. Cell Mol Biol (Noisy-le-grand) 53:49-54
Benjamin, E; Reznik, A; Benjamin, E et al. (2007) Mathematical models for conventional and microwave thermal deactivation of Enterococcus faecalis, Staphylococcus aureus and Escherichia coli. Cell Mol Biol (Noisy-le-grand) 53:42-8
Oladeinde, F O; Kinyua, A M; Laditan, A A et al. (2007) Effect of Cnidoscolus aconitifolius leaf extract on the blood glucose and insulin levels of inbred type 2 diabetic mice. Cell Mol Biol (Noisy-le-grand) 53:34-41
Sakk, Eric (2007) On the computation of molecular surface correlations for protein docking using fourier techniques. J Bioinform Comput Biol 5:915-35

Showing the most recent 10 out of 36 publications