Abstract: Provided herein are protein kinase C? inhibitors or pharmaceutical compositions thereof, for example, derivatives or analogs of bisindolylmaleimide with the general structure: Also provided are methods for treating a metabolic disease, for example, obesity and obesity-related diseases in a subject by administering one or more times at least one of the protein kinase C? inhibitors or a pharmaceutical composition thereof.

Abstract: Specific activation of the Raf-1/MEK/p42/44MAPK kinase cascade in HepG2 cells, independent of other “upstream” factors or cell growth regulation, leads to induction of LDL receptor transcription. The degree of p42/44MAPK activation determines the extent of LDL receptor induction. The present findings underscore the important and central role of the MAPK pathway in regulating low density lipoprotein receptor expression and may be of considerable potential significance for the development of new signal transduction-based approaches for the treatment of hypercholesterolemia.

Abstract: The present invention demonstrates that p38MAPK inhibitor induces low density lipoprotein receptor expression 6-8 fold, and further provides the application of such inhibitor in the treatment of hypercholesterolemia.

Abstract: The present invention demonstrates that p38MAPK inhibitor induces low density lipoprotein receptor expression 6-8 fold, and further provides the application of such inhibitor in the treatment of hypercholesterolemia.

Abstract: Specific activation of the Raf-1/MEK/p42/44MAPK kinase cascade in HepG2 cells, independent of other “upstream” factors or cell growth regulation, leads to induction of LDL receptor transcription. The degree of p42/44MAPK activation determines the extent of LDL receptor induction. The present findings underscore the important and central role of the MAPK pathway in regulating low density lipoprotein receptor expression and may be of considerable potential significance for the development of new signal transduction-based approaches for the treatment of hypercholesterolemia.

Abstract: The present invention provides a novel cis-acting regulatory element that is required for maximal induction of the human low density lipoprotein (LDL) receptor gene following depletion of cellular sterols in HepG2 cells. In vivo dimethyl sulfate footprinting of the human LDL receptor promoter before and after transcriptional induction in HepG2 cells revealed protection of the sequence 5'-GAGCTTCACGGGTTAAAAAG-3' (SEQ ID NO.1), corresponding to nucleotides -126 to -145, (referred to as FP1). Further, presence of the FP1 sequence resulted in significant enhancement of luciferase reporter gene expression (approximately 375%) in response to low levels of sterols in HepG2 cells using promoter luciferase constructs. In addition, the enhancement was markedly attenuated on nucleotide substitutions within the FP1 site. Thus, the present invention discloses a novel regulatory element, FP1, in the human LDL receptor promoter and a vector containing this element.