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Living History of Physiology
Maurice Burg , MD
Education and Professional Training
Newton High School, Newton, MA, 1948
AB cum laude, Harvard College, Cambridge, MA, 1952
MD, Harvard Medical School, Boston, MA, 1955
Research Overview
Our focus has been on the mechanisms
by which cells in the renal medulla withstand the high concentrations of
salt (NaCl) and urea that occur there when the kidney produces
concentrated urine and that are much higher than elsewhere in the body.
We initially identified some organic osmolytes (sorbitol, glycine
betaine, glycerophosphocholine (GPC) and myo-inositol) that renal
medullary cells accumulate during antidiuresis. Then, we established
tissue culture models to elucidate the protective function of the
osmolytes and the mechanisms by which they are accumulated (reviewed in
Garcia-Perez, et al, 1991 ).
We discovered the biochemical mechanisms by which the organic osmolytes
are accumulated. High NaCl increases synthesis of sorbitol from glucose
by increasing the amount of the enzyme, aldose reductase, and increases
transport of glycine betaine and myo-inositol into the cells by
increasing the number of transporters. The transcription of the aldose
reductase and transporter genes is osmotically regulated. We identified
an osmotic response element (ORE) in the aldose reductase gene and
similar elements have been identified in the transporter genes.
Currently, we are studying a transcription factor, TonEBP, whose binding
to the ORE and whose transactivating activity are increased by
hypertonicity, signaled by protein kinases, including PKA (Ferraris, et
al, 2002).
Our ongoing work also concerns the genomic stress that can occur at
extremes of high NaCl or urea and result in cell cycle arrest and
apoptosis. Recent findings are that high NaCl causes DNA damage and
impairs DNA repair, not only in cell culture, but also in vivo (Dmitrieva,
et al, 2003). Moreover, the damage is less if the cells are not
proliferating rapidly (Zhang, et al, 2002) and if the changes in NaCl
and urea concentration are slow (Cai, et al, 2002, 2004), as occurs in
the renal inner medulla in vivo.
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