title: Regulation of protein kinases and coregulatory interplay of S-100beta and serotonin transporter on serotonin levels in diabetic rat brain.
abstract: Protein kinases are critical component in the regulation of signal transduction pathways, including neurotransmitters. Our previous studies have shown that serotonin (5-HT) altered under diabetic condition was accompanied by alterations of protein kinase C-alpha (PKC-alpha) and CaMKII, and those alterations were reversed after insulin administration. The current study showed that alloxan-induced diabetic animals revealed hyperglycemia and was associated with an increase in the content of 5-HT, PKC-alpha expression and PKC activity (P < 0.05) simultaneously in striatum (ST), midbrain (MB), pons medulla (PM), cerebellum (CB), and cerebral cortex (CCX) from 7 days to 60 days. Although the 5-HT levels in hippocampus (HC) and hypothalamus (HT) were not altered, the PKC-alpha expression and PKC activity showed increases (P < 0.05) in level in HC. Insulin administration reversed all these changes to a normal level. In contrast, the in vitro study has shown that the 5-HT levels correlated with PKC-alpha expressions as well as PKC activity (P < 0.05) only in ST, MB, and CB either after induction with phorbol 12-myristate 13-acetate (PMA) or blocking with chelerythrine, whereas PM and CCX remained elevated (P < 0.05), implying a regulatory role for PKC-alpha only in ST, MB, and CB. However, our consecutive studies have shown that the 5-HT level in PM was regulated by p38-mitogen-activated protein kinase (p38-MAPK) both in vivo and in vitro, whereas the 5-HT level in CCX was coregulated by S-100beta by protein-protein interaction with serotonin transporter (SERT) via 8-bromoadenosine 3',5'-cyclic monophosphate sodium salt (8-Br-cAMP)-induced cAMP/PKAII pathway(s).
authors: Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA. rramakrishnan2@yahoo.com
authors: R
authors: R
authors: Ramakrishnan
authors: R
authors: R
authors: Sheeladevi
authors: A
authors: A
authors: Namasivayam
mesh_terms: D000090:Acetoacetates / Q000097:blood; D000496:Alloxan; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose; D001921:Brain / Q000378:metabolism*; D002254:Carbonates / Q000097:blood; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D011494:Protein Kinases / Q000145:classification / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000090:Acetoacetates; D001786:Blood Glucose; D002254:Carbonates; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C016635:acetoacetic acid; D000496:Alloxan; D011494:Protein Kinases