Patricia Ann Preisig PhD
Professor of Medicine (Nephrology) and of Cellular and Molecular Physiology
Elucidation of the acid-activated pathway that mediates the physiological response of the renal proximal tubule to the need for the kidney to excrete acid
The overall focus of our laboratory is to elucidate the acid-activated pathway that mediates the physiological response of the renal proximal tubule to the need for the kidney to excrete acid.
Extensive Research Description
A typical Western diet is acid-laden, with much of the acid load coming from the metabolism of ingested animal protein. In order to maintain systemic acid-base balance, the non-volatile portion of this acid load must be excreted by the kidney with equivalence between daily production and excretion. This is accomplished in two ways, one being regulation of base excretion (bicarbonate and citrate) and the other being regulation of acid excretion (titrated acids and ammonium). The proximal tubule of the kidney contributes to these processes by increasing proton secretion (primarily for bicarbonate reabsorption), ammonia synthesis and secretion (to buffer acid to be excreted), and citrate reabsorption and metabolism (to minimize base loss). Using both whole animal and cell culture models of a decrease in cell pH (the signal that initiates the physiological response), we are identifying and ordering the signaling intermediates that mediate the increase in apical membrane proton secretion by the Na/H antiporter isform NHE3 and citrate reabsorption by the Na-dicarboxylate co-transporter NaDC-1, and the increase in citrate metabolism and ammonia synthesis.
- Amanzadeh J, Gitomer R, Zerwekh JE, Preisig PA, Moe OW, Pak CYC, Levi M. Effect of high protein diet on stone-forming propensity and bone loss in rats. Kid Int, 64:2142-9, 2003.
- Licht C, Laghmani K, Yanagisawa M, Preisig PA*, Alpern RJ*. An autocrine role for endothelin-1 in the regulation of proximal tubule NHE3. Kid Int, 65:1320-6, 2004.
- Aruga S, Pajor A, Nakamura K, Liu L, Moe OW, Preisig PA*, Alpern RJ*. OKP cells express the Na dicarboxylate cotransporter NaDC-1. Am J Physio, 287:C64-72, 2004.
- Li S, Sato S, Yang X, Preisig PA*, Alpern RJ*. Pyk2 is a pH sensor signaling acid activation of NHE3 in OKP cells. J Clin Invest, 114:1782-9, 2004.
- Laghmani K, Sakamoto A, Yanagisawa M, Preisig PA*, Alpern RJ*. A consensus sequence in the endothelin B receptor second intracellular loop is required for NHE3 activation by endothelin-1. Am J Physio, 288:F732-9, 2005.
- Yang X, Yin H, Alpern RJ*, Preisig PA*. Rho A required for acid-induced stress fiber formation and trafficking and activation of NHE3. Am J Physiol, 293:F1054-64, 2007.
- Zhu Z, Green C, Besharse J, Alpern RJ*, Preisig PA*. The circadian gene Nocturnin is acid-regulated and modifies proximal tubule response to dietary acid intake. J Clin Invest, in revision.
- Liu L, Yanagisawa M, Alpern RJ*, Preisig PA*. Acid regulation of proximal tubule citrate transport is mediated by endothelin-1 signaling through the endothelin B receptor. Kid Int, in press
- Zerwekh JE, Zou L, Pak CYC, Moe OW, Preisig PA. Biochemical and histological assessment of alkali therapy during high animal protein intake. Bone, 45. 1004-1009, 2009
- Zhu,Z.Y., L,. Wan, A. Lin, H. Zhao, D.L. Hawkins, Jr., R.J. Alpern, and P.A. Preisig. Acid and food regulation of kidney cortical genes. In preparation