Aluminum: a high price for a surrogate?

Aluminum: A high price for a surrogate?

Aluminum, prized for its conductivityof heat and electricity, is the most abundant metal in the earth's crust. But data suggesting that too much of the metal in the body could have some role in neurological and skeletal disease have dulled aluminum's sharp image. A new study now suggests that aluminum can play the heavy in intracellular structures called microtubules, in a mechanism that may help explain aluminum's adverse effects.

Like the ubiquitous metal, microtubulesappear to be everywhere. They lend structural support to plant and animal cells, where, for example, they form the filaments called spindles that are essential for cell division. Bundles of the thread-like tubes lie inside the tails of sperm cells and along the enongated extensions of nerve cells. Microtubules apparently influence other structures inside cells as well (see photo).

Excess aluminum in the body has beenimplicated as a possible cause of the characteristic tangle of nerve fibers seen in certain disorders such as Alzheimer's disease. To examine this relationship, researchers at the University of Virginia in Charlottesville decided to follow the effect of aluminum ions on microtubules, which are repeatedly assembled and disassembled within the cell using aminoacid chains called tubulin. Normal assembly of tubulin requires magnesium ions and is affected by calcium ions; the rate of disassembly is regulated by a compound called guanosine triphosphate (GTP).

Using data from experiments on purifiedtubulin, Timothy L. MacDonald, W. Griffith Humphreys and R. Bruce Martin report in the April 10 SCIENCE that aluminum ions are taken into this system of tubulin assembly at a rate that is 10(7) times that measured for magnesium uptake. MacDonald, who calls the 10(7) figure "stunning,' says the results of the Virginia study support a theory, first proposed 10 years ago, that competition between aluminum and magnesium occurs in cells when aluminum concentrations reach abnormal levels.

Although the aluminum-induced microtubuleshave the same microscopic appearance as those formed in the presence of magnesium, aluminum as a surrogate causes problems. MacDonald told SCIENCE NEWS that "the important point of the study is that aluminum is acting as a magnesium surrogate, but, because of [structural differences in the ions], aluminum gives completely different results.' For example, microtubules from an aluminum-initiated system are less sensitive to calcium ions and have a lower rate of GTP-mediated breakdown of microtubules no longer needed.

Exactly how this disorganized microtubuleprocess is related to aluminum's neurotoxicity needs to be determined, says MacDonald, who admits he is skeptical that tubulin will prove to be aluminum's final target. The identity of that target is a mystery that MacDonald says "is going to be tough to crack, because there are so many magnesium-dependent cell components.'

Photo: Arrows point to microtubules in scavengercells called macrophages. Recent studies at New York's Columbia University --reported in the April PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (Vol.84, No.7)--suggest that microtubules affect the movement and shape of enzyme-containing structures called lysosomes, seen here as large, darkly stained bodies.