The effect of protein kinase C-delta knockdown on anti-free radical enzyme and neuropeptide Y gene expression in phenylpropanolamine-treated rats.
Hypothalamic neuropeptide Y (NPY) has been reported to involve in regulating behavioral response of phenylpropanolamine (PPA), a sympathomimetic agent. This study explored if protein kinase C (PKC)-delta signaling participated in this regulation. Moreover, possible roles of anti-free radical enzyme catalase (CAT) and nitrogen oxide synthase (NOS) were also examined. Rats were treated daily with PPA for 4 days. Changes in food intake and hypothalamic NPY, PKCdelta, CAT, and NOS contents were assessed and compared. Results showed that PKCdelta and CAT increased during PPA treatment, which were concomitant with decreases in NPY content and food intake, while the change of NOS was expressed differently. Moreover, PKCdelta knockdown could modify PPA anorexia as well as NPY and CAT expression, while NOS expression remained unchanged. Furthermore, pre-treatment with NOS inhibitor could modify both PPA anorexia and NPY content. It is suggested that PKCdelta participates in the anorectic response of PPA via the modulation of NPY and CAT, while NOS contribute to this modulation via a different mechanism during PPA treatment. Results provide molecular mechanism of NPY-mediated PPA anorexia and may aid the therapeutic research of PPA and other anti-obesity drugs.
Department of Physiology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City, Taiwan, China. dykuo@csmu.edu.tw
Dong-Yih
DY
Kuo
Shun-Fa
SF
Yang
Shu-Chen
SC
Chu
Chin-Hsiu
CH
Chen
Pei-Ni
PN
Chen
Yih-Shou
YS
Hsieh
D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D002374:Catalase / Q000378:metabolism*; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005609:Free Radicals / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010665:Phenylpropanolamine / Q000008:administration & dosage*; D051745:Protein Kinase C-delta / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D005609:Free Radicals; D009478:Neuropeptide Y; D009569:Nitric Oxide; D010665:Phenylpropanolamine; D002374:Catalase; D052248:Nitric Oxide Synthase Type I; D051745:Protein Kinase C-delta