Genomes and Genes
Affiliation: University of Calgary
- Developing PAR1 antagonists: minding the endothelial gapRithwik Ramachandran
Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N4N1, Canada
Discov Med 13:425-31. 2012..This review provides an overview of the proteinase activated receptor family and focuses on the role of PAR1 in regulating the endothelial barrier integrity and its implication on developing PAR antagonists for anti-platelet therapy...
- Targeting proteinase-activated receptors: therapeutic potential and challengesRithwik Ramachandran
Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Alberta T2N 4N1, Canada
Nat Rev Drug Discov 11:69-86. 2012..In this Review we summarize the mechanisms by which PARs modulate cell function and the roles they can have in physiology and diseases. Furthermore, we provide an overview of possible strategies for developing PAR antagonists...
- Neutrophil elastase acts as a biased agonist for proteinase-activated receptor-2 (PAR2)Rithwik Ramachandran
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada
J Biol Chem 286:24638-48. 2011..Our data illustrate a new mode of PAR regulation that involves biased PAR(2) signaling by neutrophil elastase and a disarming/silencing effect of cathepsin-G and proteinase-3...
- Insulin modulates protease-activated receptor 2 signaling: implications for the innate immune responseEric Hyun
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
J Immunol 184:2702-9. 2010..Our data point to an anti-inflammatory action of insulin that targets the acute innate inflammatory response triggered by PAR(2)...
- Agonist-biased signaling via proteinase activated receptor-2: differential activation of calcium and mitogen-activated protein kinase pathwaysRithwik Ramachandran
Department of Pharmacology and Therapeutics and Medicine, University of Calgary, Calgary, AB T2N4C2, Canada
Mol Pharmacol 76:791-801. 2009..Thus, PAR(2) can signal to multiple pathways that are differentially triggered by distinct proteinase-revealed TLs or by synthetic signal-selective activating peptides...
- Derivatized 2-furoyl-LIGRLO-amide, a versatile and selective probe for proteinase-activated receptor 2: binding and visualizationMorley D Hollenberg
Department of Pharmacology and Therapeutics, University of Calgary Faculty of Medicine, 3330 Hospital Drive NW, Calgary, AB T2N4N1, Canada
J Pharmacol Exp Ther 326:453-62. 2008..We conclude that ornithine-derivatized 2fLI peptides are conveniently synthesized PAR2 probes that will be of value for future studies of receptor binding and visualization...
- Proteinase-activated receptors (PARs): differential signalling by kallikrein-related peptidases KLK8 and KLK14Rithwik Ramachandran
Department of Physiology and Pharmacology, University of Calgary, Faculty of Medicine, AB, Canada
Biol Chem 393:421-7. 2012..Thus, KLK8 and KLK14 can signal differentially via the PARs to affect tissue function...
- Implantation serine proteinase 1 exhibits mixed substrate specificity that silences signaling via proteinase-activated receptorsNavneet Sharma
Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada
PLoS ONE 6:e27888. 2011..We observed that ISP1 silenced enzyme-triggered PAR signaling by receptor-disarming. This PAR-disarming action of ISP1 may be important for embryo development and implantation...
- Proteinases as hormones: targets and mechanisms for proteolytic signalingKristina K Hansen
Proteinases and Inflammation Network, University of Calgary Faculty of Medicine, Calgary T2N 4N1, AB, Canada
Biol Chem 389:971-82. 2008..Further, proteinases can be considered as physiologically relevant 'hormone-like' messengers that can convey signals locally or systemically either via PARs or by other mechanisms...
- MicroRNA profiling reveals new aspects of HIV neurodegeneration: caspase-6 regulates astrocyte survivalFarshid Noorbakhsh
Department of Medicine Neurology, University of Alberta, Edmonton, AB, Canada
FASEB J 24:1799-812. 2010..Overall, these data point to previously unrecognized alterations in miRNA profile in the brain during HIV infection, which contribute to cell death through dysregulation of cell death machinery...
- Mechanisms behind the anti-inflammatory actions of insulinEric Hyun
Department of Physiology and Pharmacology, University of Calgary, Canada
Crit Rev Immunol 31:307-40. 2011..Further, we discuss how the anti-inflammatory action of insulin bears on our current understanding of the pathophysiology and complications of both type 1 and type 2 diabetes...
- TRPM8 activation attenuates inflammatory responses in mouse models of colitisRithwik Ramachandran
Department of Physiology and Pharmacology, Inflammation Research Network, Snyder Institute for Chronic Diseases Department of Pathology and Laboratory Medicine, and Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, AB, Canada T2N 4N1
Proc Natl Acad Sci U S A 110:7476-81. 2013..Our data document an anti-inflammatory role for TRPM8 activation, in part due to an inhibiton of neuropeptide release, pointing to a novel therapeutic target for colitis and other inflammatory diseases...
- Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancerMorley D Hollenberg
Proteinases and Inflammation Network, Department of Pharmacology and Therapeutics, University of Calgary Faculty of Medicine, Calgary T2N 4N1, AB, Canada
Biol Chem 389:643-51. 2008....
- Proteinase-activated receptor-2 activating peptides: distinct canine coronary artery receptor systemsMahmoud Saifeddine
Department of Pharmacology and Therapeutics, University of Calgary Faculty of Medicine, 3330 Hospital Drive N W, Calgary, Alberta, Canada
Am J Physiol Heart Circ Physiol 293:H3279-89. 2007....