V-ATPases Subunit D2 Is Critical For Acdification And Bone Resorption.
Funder
National Health and Medical Research Council
Funding Amount
$531,264.00
Summary
Overproduction and excessive activity of osteoclasts underlines many lytic bone disorders such as osteoporosis, Paget's disease and tumor-induced bone loss. The vacuolar proton pump (V-ATPase) located on the plasma membrane of the osteoclast is critical for osteoclastic bone resorption and, therefore represents a potential molecular target for the discovery of novel bone anti-resorptive agents. The proposed project addresses the fundamental role of the V-ATPase in osteoclast differentiation, aci ....Overproduction and excessive activity of osteoclasts underlines many lytic bone disorders such as osteoporosis, Paget's disease and tumor-induced bone loss. The vacuolar proton pump (V-ATPase) located on the plasma membrane of the osteoclast is critical for osteoclastic bone resorption and, therefore represents a potential molecular target for the discovery of novel bone anti-resorptive agents. The proposed project addresses the fundamental role of the V-ATPase in osteoclast differentiation, acidification and bone resorption. Understanding the molecular and cellular mechanisms by which V-ATPases regulate osteoclast function and bone resorption will facilitate the development of novel and selective inhibitors for the treatment of lytic bone disordersRead moreRead less
Regulation Of The Cardiac Sodium/proton Exchanger During Ischaemia, Reperfusion And Preconditioning
Funder
National Health and Medical Research Council
Funding Amount
$101,000.00
Summary
Heart attacks are currently treated with drugs to dissolve the clot in the coronary artery or by catheterisation with the aim of restoring blood flow to the ischaemic heart muscle. If restoration of blood flow occurs soon after the heart attack, the ischaemic region can recover completely. However if treatment is delayed, the ischaemic region may not recover. This project concerns the mechanisms that are involved in the myocardial damage which occurs after moderate periods of ischaemia. A transp ....Heart attacks are currently treated with drugs to dissolve the clot in the coronary artery or by catheterisation with the aim of restoring blood flow to the ischaemic heart muscle. If restoration of blood flow occurs soon after the heart attack, the ischaemic region can recover completely. However if treatment is delayed, the ischaemic region may not recover. This project concerns the mechanisms that are involved in the myocardial damage which occurs after moderate periods of ischaemia. A transport protein, the sodium-proton exchanger, is involved in recovery and if its action is blocked with an inhibitory drug, recovery of the ischaemic myocardium is improved. However clinical trials of the drug in humans have given variable results. We are investigating the regulation of this exchanger and believe that such information is essential to the efficient use of the inhibitory drugs in humans and may identify other pathways to improving recovery after ischaemia.Read moreRead less