Serum, liver, and kidney proteomic analysis for the alloxan-induced type I diabetic mice after insulin gene transfer of naked plasmid through electroporation.
Gene therapy has been reported to be effective in treating diabetes mellitus (DM), while little has been found out about the functional protein changes since. The liver and kidney play important roles in glucose absorption, metabolism, and excretion. Changes in the two organs may reflect pathologic alterations during DM, while the serum has a direct connection with most organs and pathological changes. We used alloxan to induce diabetic mice, electrotranferred the insulin gene into their sural muscles, and discovered that their blood glucose decreased to normal level. Consequently, proteomic approaches were applied to evaluate protein changes in the liver, kidney, and serum of normal, diabetic, and gene transferred mice. Forty-three proteins were found either up-regulated or down-reglulated in the liver, kidney, and serum of the alloxan-induced type I diabetic mice. Only five proteins in the liver, five proteins in the kidney, and seven proteins in the serum of diabetic mice were found to be back-regulated to normal levels after gene transfer. These back-regulated proteins are involved in lipid and glucose metabolism, associated with phosphorylation, signal transduction, oxidation, and immune inflammation. Our findings might promote a better understanding for the mechanism of DM, and provide novel targets for estimating the effects of gene therapy.
Diao
Wei-Fei
WF
Department of Biochemistry and Molecular Biology, College of Life Sciences, National Laboratory of Protein Engineering and Plant Genetic Engineering, Peking University, Beijing, People's Republic of China.
Chen
Wei-Qiang
WQ
Wu
Yuanyuan
Y
Liu
Peng
P
Xie
Xiao-Lei
XL
Li
Shuai
S
Shen
Ping-Ping
PP
Ji
Jianguo
J
D000818:Animals; D001798:Blood Proteins / Q000032:analysis*; D030562:Databases, Protein; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D015180:Electrophoresis, Gel, Two-Dimensional; D018274:Electroporation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D015151:Immunoblotting; D007328:Insulin / Q000235:genetics*; D007668:Kidney / Q000737:chemistry*; D008099:Liver / Q000737:chemistry*; D051379:Mice; D010449:Peptide Mapping; D010957:Plasmids / Q000235:genetics; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013194:Staining and Labeling
D001798:Blood Proteins; D007328:Insulin