Roles of protein kinase Calpha isozyme in the regulation of oxidative stress and neuropeptide Y gene expression in phenylpropanolamine-mediated appetite suppression.
Hypothalamic neuropeptide Y (NPY) is an appetite stimulant in the brain. Although regulation of NPY expression has been reported to contribute to the appetite-suppressing effect of phenylpropanolamine (PPA), it is still unknown if protein kinase C (PKC) is involved in this effect. Rats were daily treated with PPA for 4 days. Changes in food intake, hypothalamic NPY, PKC, and proopiomelanocortin (POMC) mRNA levels were assessed and compared. Results showed that the NPY gene was down-regulated following PPA treatment, which was parallel with the decrease of feeding. Moreover, several isotypes of PKC mRNA level (alpha, betaI, betaII, gamma, delta, eta, lambda, epsilon, and zeta) were changed. Among these, alpha, delta, and lambda PKC were up-regulated along with POMC gene expression which coincided with down-regulation of the NPY gene. To further determine if PKCalpha was involved, infusions of antisense oligonucleotide into the cerebroventricle were performed at 1 h before daily PPA treatment in free-moving rats. Results showed that PKCalpha knock-down could modify both anorexia induced by PPA and the NPY mRNA levels. Moreover, PKCalpha knock-down could also modify superoxide dismutase (SOD) gene expression. It is suggested that PKCalpha participates in the regulation of PPA-mediated appetite suppression via the modulation of NPY and SOD gene expression.
Kuo
Dong-Yih
DY
Department of Physiology, Chung Shan Medical University, Taiwan, China. dykuo@csmu.edu.tw
Yang
Shun-Fa
SF
Chu
Shu-Chen
SC
Chen
Chin-Hsiu
CH
Hsieh
Yih-Shou
YS
D000704:Analysis of Variance; D000818:Animals; D001066:Appetite / Q000187:drug effects; D001067:Appetite Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular / Q000379:methods; D007527:Isoenzymes / Q000502:physiology; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage; D018384:Oxidative Stress / Q000502:physiology*; D010665:Phenylpropanolamine / Q000494:pharmacology*; D051571:Protein Kinase C-alpha / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D001067:Appetite Depressants; D007527:Isoenzymes; D009478:Neuropeptide Y; D020319:Oligodeoxyribonucleotides, Antisense; D010665:Phenylpropanolamine; D051571:Protein Kinase C-alpha; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2