During the past 4 years since the last comprehensive progress report we have proved that GI hormones directly influence growth of GI mucosa and that gastrin is an important physiological stimulator of growth of oxyntic gland, small intestinal and colonic mucosa. In addition we have worked out much of the biochemical response involved in the mechanism of gastrin's stimulation of the pleiotypic response. We have also estalished that the pituitary and growth hormone play a significant role in regulating endogenous gastrin levels. This work will be extended in the current proposal by pursuing the following areas: (1) examination of additional GI peptides and hormones (2) determination of the role of parasympathetic innervation in regulating growth of GI mucosae, (3) determination of inter-relationships of ACTH, corticol, growth hormone and gastrin regulating growth of FI mucosae, (4) development of a receptor assay for gastrin binding to trophic activity and cyclic nucleotides, (5) mucosal tissue from patients with gastric ulcer, pernicious anemia, atrophic gastritis of cancer will be cultured and its growth and gastrin binding characteristics studied, (6) the identity of protein whose synthesis is stimulated by gastrin will be studied using polyacrylamide SDS gel electrophoresis. The overall objective of this project is to define and understand the factors regulating the growth of gastrointestinal mucosa with a special emphasis on gastrointestinal hormones.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Method to Extend Research in Time (MERIT) Award (R37)
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University of Tennessee Health Science Center
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Ray, Ramesh M; Bavaria, Mitul; Johnson, Leonard R (2015) Interaction of polyamines and mTOR signaling in the synthesis of antizyme (AZ). Cell Signal 27:1850-9
Bhattacharya, Sujoy; Ray, Ramesh M; Johnson, Leonard R (2014) Cyclin-dependent kinases regulate apoptosis of intestinal epithelial cells. Apoptosis 19:451-66
Ray, Ramesh M; Bhattacharya, Sujoy; Bavaria, Mitul N et al. (2014) Spermidine, a sensor for antizyme 1 expression regulates intracellular polyamine homeostasis. Amino Acids 46:2005-13
Ray, Ramesh M; Johnson, Leonard R (2014) Regulation of intestinal mucosal growth by amino acids. Amino Acids 46:565-73
Bavaria, Mitul N; Jin, Shi; Ray, Ramesh M et al. (2014) The mechanism by which MEK/ERK regulates JNK and p38 activity in polyamine depleted IEC-6 cells during apoptosis. Apoptosis 19:467-79
Ray, Ramesh M; Bhattacharya, Sujoy; Bavaria, Mitul N et al. (2014) Antizyme (AZ) regulates intestinal cell growth independent of polyamines. Amino Acids 46:2231-9
Bhattacharya, Sujoy; Chaum, Edward; Johnson, Dianna A et al. (2012) Age-related susceptibility to apoptosis in human retinal pigment epithelial cells is triggered by disruption of p53-Mdm2 association. Invest Ophthalmol Vis Sci 53:8350-66
Ray, Ramesh M; Li, Chunying; Bhattacharya, Sujoy et al. (2012) Spermine, a molecular switch regulating EGFR, integrin ýý3, Src, and FAK scaffolding. Cell Signal 24:931-42
Ray, Ramesh M; Viar, Mary Jane; Johnson, Leonard R (2012) Amino acids regulate expression of antizyme-1 to modulate ornithine decarboxylase activity. J Biol Chem 287:3674-90
Bhattacharya, Sujoy; Ray, Ramesh M; Chaum, Edward et al. (2011) Inhibition of Mdm2 sensitizes human retinal pigment epithelial cells to apoptosis. Invest Ophthalmol Vis Sci 52:3368-80

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