http://jpet.aspetjournals.org Journal of Pharmacology and Experimental Therapeutics RSS feed -- recent PERSPECTIVES IN PHARMACOLOGY articles 1521-0103 Journal of Pharmacology and Experimental Therapeutics 0022-3565 http://jpet.aspetjournals.org/icons/banner/title.gif http://jpet.aspetjournals.org http://jpet.aspetjournals.org/cgi/content/short/327/3/602?rss=1 The involvement of glucose in fundamental metabolic pathways represents a core element of biology. Late in the 20th century, a unique glucose-derived signal was discovered, which appeared to be involved in a variety of cellular processes, including mitosis, transcription, insulin signaling, stress responses, and potentially, Alzheimer's disease, and diabetes. By definition, this glucose-fed signaling system was a post-translational modification to proteins. However, unlike classical cotranslational N-glycosylation occurring in the endoplasmic reticulum and Golgi apparatus, this process occurs elsewhere throughout the cell in a highly dynamic fashion, similar to the quintessential post-translational modification, phosphorylation. This more recently described post-translational modification, the β-O-linkage of N-acetylglucosamine (i.e., O-GlcNAc) to nucleocytoplasmic proteins, represents an under-investigated area of biology. This signaling system operates in all of the tissues examined and seems to have persisted throughout all multicellular eukaryotes. Thus, it comes with little surprise that O-GlcNAc signaling is an integral system and viable target for biomedical investigation. This system may be a boundless source for insight into a variety of diseases and yield numerous opportunities for drug design. This Perspective will address recent insights into O-GlcNAc signaling in the cardiovascular system as a paradigm for its involvement in other biological systems.

]]> 2008-11-12 info:doi/10.1124/jpet.108.143263 American Society for Pharmacology and Experimental Therapeutics 3 327 609 2008-12-01 602 PERSPECTIVES IN PHARMACOLOGY http://jpet.aspetjournals.org/cgi/content/short/327/2/300?rss=1 Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. However, its use is limited by side effects in normal tissues, particularly the kidneys. Recent studies, using both in vitro and in vivo experimental models, have suggested a critical role for p53 in cisplatin nephrotoxicity. The signaling pathways upstream and downstream of p53 are being investigated and related to renal cell injury and death. Along with the mechanistic studies, renoprotective approaches targeting p53 have been suggested. Further research may integrate p53 signaling with other nephrotoxic signaling pathways, providing a comprehensive understanding of cisplatin nephrotoxicity and leading to the development of effective renoprotective strategies during cancer therapy.

]]> 2008-10-17 info:doi/10.1124/jpet.108.139162 American Society for Pharmacology and Experimental Therapeutics 2 327 307 2008-11-01 300 PERSPECTIVES IN PHARMACOLOGY