title: Knocking down the transcript of protein kinase C-lambda modulates hypothalamic glutathione peroxidase, melanocortin receptor and neuropeptide Y gene expression in amphetamine-treated rats.
abstract: It has been reported that neuropeptide Y (NPY) contributes to the behavioral response of amphetamine (AMPH), a psychostimulant. The present study examined whether protein kinase C (PKC)-λ signaling was involved in this action. Moreover, possible roles of glutathione peroxidase (GP) and melanocortin receptor 4 (MC4R) were also examined. Rats were given AMPH daily for 4 days. Hypothalamic NPY, PKCλ, GP and MC4R were determined and compared. Pretreatment with α-methyl-para-tyrosine could block AMPH-induced anorexia, revealing that endogenous catecholamine was involved in regulating AMPH anorexia. PKCλ, GP and MC4R were increased with maximal response on Day 2 during AMPH treatment, which were concomitant with the decreases in NPY. cAMP response element binding protein (CREB) DNA binding activity was increased during AMPH treatment, revealing the involvement of CREB-dependent gene transcription. An interruption of cerebral PKCλ transcript could partly block AMPH-induced anorexia and partly reverse NPY, MC4R and GP mRNA levels to normal. These results suggest that PKCλ participates in regulating AMPH-induced anorexia via a modulation of hypothalamic NPY gene expression and that increases of GP and MC4R may contribute to this modulation. Our results provided molecular evidence for the regulation of AMPH-induced behavioral response.
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University Hospital, Taiwan, R.O.C.
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Chu
authors.forename: Chin-Hsiu
authors.initials: CH
authors.lastname: Chen
authors.forename: Dong-Yih
authors.initials: DY
authors.lastname: Kuo
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D016375:Antisense Elements (Genetics) / Q000008:administration & dosage; D001067:Appetite Depressants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001665:Binding Sites; D002395:Catecholamines / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000201:enzymology; D007276:Injections, Intraventricular; D007527:Isoenzymes / Q000172:deficiency* / Q000235:genetics; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000172:deficiency* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019805:alpha-Methyltyrosine / Q000494:pharmacology; D000099293:Protein Kinase C-lambda
chemical_list: D000661:Amphetamine; D016375:Antisense Elements (Genetics); D001067:Appetite Depressants; D002395:Catecholamines; D000697:Central Nervous System Stimulants; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D005979:Glutathione Peroxidase; D007527:Isoenzymes; D009478:Neuropeptide Y; D011493:Protein Kinase C; D012333:RNA, Messenger; D044105:Receptor, Melanocortin, Type 4; D014446:Tyrosine 3-Monooxygenase; D019805:alpha-Methyltyrosine; D000099293:Protein Kinase C-lambda; C508137:Creb1 protein, rat