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In the past year, high serum suPAR levels also have been found to predict kidney and multiple organ failure in hospitalized patients with COVID-19.
“FSGS is a particularly insidious kidney disease. In many patients, it inexorably leads to kidney failure and we don’t have much to offer to stop it, and worse still, in most patients it recurs after a kidney transplant, leading to failure of the transplanted kidney,” said Stuart E. Dryer, Moores Professor of biology and biochemistry, with a joint appointment as a professor of biomedical sciences in the UH College of Medicine. Dryer is working to identify possible new therapeutic targets for chronic kidney disease, particularly focal segmental glomerulosclerosis, and his very first place to look is the suPAR protein.
Greater suPAR levels in blood induce oxidative stress in the glomeruli, the tiny filtering units inside the kidney, and discharge oxygen-free radicals that attack cell membranes and disrupt ion channels, causing a rise in calcium levels within the cell. In many conditions, higher suPAR levels have bad prognostic indications.
“Basically, if you’re sick and your serum suPAR levels are high, you’re in trouble,” said Dryer. To block the action of suPAR, he’s examining a drug that has already undergone clinical trials for unrelated conditions, such as Alzheimer’s disease. A $1.4 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases affirms his job.
It started as a very lucky guess actually, but we’ve shown it in a dish, that we can take isolated cells and if we treat them with suPAR they develop oxidative stress and if we add this drug, that doesn’t happen.”
Stuart E. Dryer, Professor, UH College of Medicine
Dryer’s other favourite target is an ion channel protein known as TRPC6 (Transient Receptor Potential Cation Channel Subfamily C Member 6). Excessive activation of TRIPC6 causes FSGS and suPAR greatlyg raises the action of TRPC6.
“My lab has demonstrated the suPAR and TRPC6 are connected to one another,” said Dryer. “If you add suPAR to cells, TRPC6 gets more active,” said Dryer. “Now we need to understand better how TRPC6 actually works in related kidney cells.”
University of Houston