Role of protein kinase Cµ isoform expression in dimethylhydrazine-induced             vascular endothelial proliferation.
1,2-Dimethylthdrazine (DMH) has been known to induce vascular neoplasms,             such as malignant endothelioma, in animal experiments through the induction of             abnormal proliferation of human umbilical vein endothelial cells (HUVECs). We             studied the effect of protein kinase C (PKC) isoforms on DMH-induced abnormal             proliferation of vascular endothelium to identify the isoforms with higher relevance.             The study was conducted with pure culture HUVECs in a control group and a 1x10-9             M DMH-treated group. The mRNA and protein expression of PKC isoforms in DMH-treated             HUVECs was evaluated by reverse transcription-polymerase chain reaction and western             blotting. DMH-induced PKC production was detected by a PKC activity assay. To             investigate the role of the PKC isoforms in DMH-induced abnormal HUVEC proliferation,             we modulated PKCµ expression in DMH-treated HUVECs using small interfering RNA.             We determined the expression of 11 PKC isoforms by PCR analysis in both the control             and DMH-treated groups, and the results were statistically analyzed to detect             any differences. According to the results, both groups expressed 6 out of 11 isoforms.             Expression of PKCµ was significant in the DMH-treated group, and downregulation             of PKCµ inhibited DMH-induced abnormal HUVEC proliferation. The PKCµ isoform is             believed to be important in the abnormal growth of vascular endothelial cells             induced by DMH, and this was confirmed by an objective siRNA experiment, which             showed a clear decrease in PKCµ expression. Therefore, it is believed that PKCµ             is a key factor in the abnormal proliferation of vascular endothelial cells, and             these results can be used as fundamental research data for abnormal vessel development             or the embryologic mechanisms of vessel development.
Department of Plastic and Reconstructive Surgery, School of Medicine,                     Pusan National University, Busan 602-739, Republic of Korea.
Subong
S
Nam
Soojong
S
Choi
Jaewoo
J
Lee
Joohyoung
J
Kim
Jisun
J
Song
Yongchan
Y
Bae
D019813:1,2-Dimethylhydrazine / Q000009:adverse effects*; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation; D057075:Enzyme Assays; D015971:Gene Expression Regulation, Enzymologic; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D043925:Angiogenesis Inducing Agents; D007527:Isoenzymes; D034741:RNA, Small Interfering; C089212:protein kinase D; D011493:Protein Kinase C; D019813:1,2-Dimethylhydrazine