In conclusion, PER1 transcription in cervical cancer cells is mainly uncoupled from promoter methylation and may primarily be related to the availability and interactions of crucial positive or negative trans-activating transcription factors targeting at their respective WEHI-539 hydrochloride in the hypomethylated zone located in the PER1 promoter.
Acknowledgments
We thank Y.-F. Kao for contribution to the BGS protocol and Dr. C.-J. Hong of the Taipei General Veterans Hospital for the use of the real-time thermal cycler. This work was supported by the intramural grants (V95S4-003 and -014) of the Taipei Veterans General Hospital awarded to KBC.
Keywords
Folate; Catalase; Superoxide dismutase; Conjugation; Macrophages; Inflammatory diseases
Recently, the Low laboratory and others have demonstrated that the folate receptor is overexpressed on activated macrophages in arthritic tissue, [14] and [15] and that folate-conjugated proteins can be delivered to the cytoplasm of target cells via folate receptor-mediated endocytosis [16] and [17]. Based on this evidence, conjugation of folate to SOD and CAT could potentially target these enzymes to activated macrophages and enhance their efficacy in treating inflammatory diseases. In this communication, we demonstrate that folate can be readily conjugated to CAT and SOD with high efficiency, and that conjugation of folate does not lower the activity of these enzymes. We also demonstrate that conjugation of folate enhances the ability of CAT and SOD to scavenge ROS produced by activated macrophages. Based on these observations, we anticipate that folate-conjugated CAT and SOD will have numerous applications for the treatment of rheumatoid arthritis and other inflammatory diseases.
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