Dehydration, low blood pressure, septic shock, trauma or removing a kidney for transplantation can temporarily halt or reduce blood and oxygen supplies, says Dr. Zheng Dong, cell biologist at the Medical College of Georgia.
Ischemia leads to cell suicide or apoptosis, particularly in the energy-consuming tubular cells of the kidneys, he says. Fifty percent mortality rates from resulting ischemic renal failure haven't changed in nearly as many years, Dr. Dong says.
Tubular cells which have the daunting daily task of reabsorbing nearly 50 gallons of usuable fluid volume, including salt and glucose the kidneys filter from the blood every 24 hours are particularly vulnerable to apoptosis and injury, Dr. Dong says.
"They are highly energy-dependent," he says. "That is why when you shut off the blood supply, these cells are quickly, irreversibly damaged and they die." Tubular cell injury and death is why kidneys are so vulnerable, for example in critically ill patients.
It's in this oxygen-deprived environment that two proteins, Bid and Bax each a known killer in its own right are activated and may partner to induce cell death. The killing proteins are pervasive, particularly in the kidneys, says Dr. Dong, who recently received a $1 million grant from the National Institute of Diabetes & Digestive & Kidney Diseases, to better understand their role in cell death during ischemic renal failure.
In both cell culture and animal models of ischemic renal injury, Dr. Dong and his colleagues have found Bid is cleaved or cut, releasing active fragments. Although he still doesn't know what cuts Bid, that act enables the protein to move from its usual place in the outer region of the cell to inside its powerhouses or mitochondria.
Contact: Toni Baker
Medical College of Georgia