Ionic homeostasis regulation and ischemic neurodegeneration
Office Phone: (608) 263-4060, (608) 263-4011
The research interest of my laboratory is to understand molecular mechanisms of ischemic cell death in the central nervous system (CNS) and identify therapeutic targets for stroke treatment. We focus on studying of ion homeostasis disruption during cerebral ischemia and roles of ion transport proteins in ischemic brain damage.
Na-K-Cl cotransporters and Na/H exchanger represent two families of integral membrane proteins that regulate ion homeostasis and cell volume. Our studies demonstrated that expression of the Na-K-Cl cotransporter protein in rat brain is up-regulated after cerebral ischemia. Pharmacological inhibition of the cotransporter activity significantly reduces neuronal death after ischemia. We recently found that the Na-K-Cl cotransporters contribute to glutamate-mediated excitotoxicity in cultured neurons. In addition, Na/H exchanger appears to play a role in ischemic damage in astrocytes and neurons. We take pharmacological inhibition and transgenic knockout approaches to further investigate the underlying mechanisms.
- Luo, J., H. Chen, D.B. Kintner, G.E. Shull, and D. Sun. 2005. Decreased neuronal death in Na+/H+ exchanger isoform 1-null mice following in vitro and in vivo ischemia. J. Neurosci. In press.
- Chen, H., J. Luo, D. Kintner, G. Shull, and D. Sun. 2005. Na+-dependent chloride transporter (NKCC1)-null mice exhibit less gray and white matter damage after focal cerebral ischemia. J. Cereb. Blood Flow and Metab. 25: 54-66.
- Lenart, B., D.B. Kintner, G.E. Shull and D. Sun. 2004. Na-K-Cl cotransporter-mediated intracellular Na+ accumulation affects Ca2+ signaling in astrocytes in an in vitro ischemic model. J. Neurosci. 24: 9585-9597
- Kintner, D.B., B. Lenart, A.J. Ballard, J.W. Meyer, L.L. Ng, G.E. Shull and D. Sun. 2004. Increased tolerance to oxygen glucose deprivation in astrocytes from Na+/H+ exchanger isoform 1 null mice. Am. J. Physiol. Cell Physiol. 287: C12-C21.
- Wang H., Y. Yan, D.B. Kintner, C. Lytle, and D. Sun. 2003. GABA-mediated trophic effect on oligodendrocytes requires Na-K-Cl cotransporter activity. J. Neurophysiol. 90: 1257-1265.
- Beck, J., B. Lenart, D.B. Kintner, and D. Sun. 2003. Na-K-Cl cotransporter contributes to glutamate mediated excitotoxicity. J. Neurosci. 23: 5061-5068
- Schomberg, S.L., J. Bauer, D.B. Kintner, G. Su, A. Flemmer, B. Forbush, and D. Sun. 2003. Cross-talk between the GABAA receptor and the Na-K-Cl cotransporter is mediated by intracellular Cl-. J. Neurophysiol. 89: 159-167.
- Su, G., D.B. Kintner, M. Flagella, G.E. Shull, and D. Sun. 2002. Astrocytes from Na-K-Cl cotransporter (NKCC1) null mice exhibit an absence of swelling and decrease in EAA release. Am. J. Physiol. 282: C1147-C1160.