PSU Magazine Summer 1990

'\ L him , but he cut me short . ·If I wanted someone who would be valuable to me right now, I wouldn 't hire you, he sai d .· "As it turned out , he had some grant money from the Dental Association , and said I could work for him , as long as I studied calc ium . That 's how calcium became my fi e ld . I didn't know back in 1975 it would come thi s far." During hi s graduate years at the Univer– sity of Rochester, Abramson completed a National Science Foundation fellowship (70-72) and a National Institute of Health traineeship (75-76). Hi s Muscul ar Dys– trophy Association Postdoctoral Fe ll owship (77-79) included research on the reconstitu– tion of the calcium pump and its tryptic fragments into artific ial membranes. In 1979, he moved to Portland with hi s wife, Kathy, and infant daughter, to accept a position as ass istant professor at Portl and State, where hi s research interest continued in membrane biophys ics and biochemistry. He was appointed assoc iate professor in 1984 and professor in 1989. It was a chance discovery with heavy metals that started Abramson down the path to the elusive calcium-release protein... A bramson's first major discovery came in 1983. As a part of PSU 's Environmental Sciences and Resources Doctoral Program , he was carrying out experiments usi ng heavy metals (zi nc, mercury, cadmium and silver) which are environmentally tox ic substances. 'There had been several cases of large popul ati on poisonings in Japan and the Mideast , and interest in the area was runnjng high. Quite by accident , I discovered that this calci um-release membrane system (sarcoplasmic reticulum) was highly sensitive to low levels of heavy metal s. And , in the case of mercury, very small concentra– ti ons caused the calc ium to rush out of the membrane much faster than anyone else had ever observed. I RESEARCH ..Rather than brush thi s off as an anomaly, I began to suspect there was some interaction go ing on wi th the ca lc ium-release protein everyone was look ing for." That same year, Abramson published a major article on hi s work. He continued studying thi s phenomena over a period of years, and was finally able to conclude that there was a speci fie locat io n on a membrane– bound protein that interacted with these heavy metals. He was then able to develop probes needed to begin isolating individual proteins. Another major publication in 1986 described how ox idat ion could stimulate the release of calci um from the sarcoplasmic reticulum. Abramson went on to identify the site of calci um release and the specific protein which causes the trigger reaction. He published two articles in December 1989, and presented hi s findings to a meeti ng of the Biophys ical Society in February 1990. "I expect some controversy over thi s,,. Abramson admits. "Another research group claimed to have isolated the calcium-re lease protein thi s past year. When I heard about their discovery, I was disappointed and exc ited . Disappo inted that I hadn't yet fo und the protei n, and excited that someone had found it after all these years. " But on reading their report, I d iscovered they had isolated an entire ly different protein from the one which I was studying. My attempts to duplicate their study resulted in hi gher than acceptab le levels of contami– nation, which means the protein was not very pure. There are currentl y three theories describing the molecular mechanism underlying calcium release from sarcoplas– mic reticulum , according to Abramson. He believes that the theory he has developed, which invo lves an oxidation reaction , is the con-ect one. "You don't go on with your work just to prove someone e l e is wrong," he cautions. "But you use all the research as a base for taking new directions and moving on." It was a chance discovery with heavy metals that started Abramson down the path to the elusive calcium- release protein in (Chris Normandin, afree-lance public relations writer in Portland, is a regular conrributor ro PSU Magazine.) ske letal muscle. and it was a chance reading that brought him into the heart disease are na . A recognized problem in heart di sease is ischemia, lack of adequate oxyge n to parts of the heart caused by arteri osc lerosis or blocked arteries. The conditi on is currentl y treated wi th by-pass surgery, balloon inflati on therapy or calcium-blocki ng agents that dilate the arteries. Once thi s is done , the area sudden ly gets more oxygen. which can cause damage to cardiac mu scle. ca lled reperfusion damage. " I fo und some work being done in England , in which the researchers were looking at a chemical compound that mimics reperfusion damage in the whole heart,,. says Abramson ...I was studying the same compound , but examining its effect on isolated membranes. It turns out th at reperfusion damage may be caused by damage to the calcium-re lease prote in that we recentl y identified ... Another tie into Abramson's research has come on a loca l level. For the past two years, he has co ll aborated with Dr. Jeffrey Hosenpud of the Oregon Health Sciences Universi ty, and Dr. Leonard Simpson of the PSU Biology Department. on a study funded by the American Cancer Society. Together, they are looking at adriamycin. a commonl y used anti -cancer drug . Whil e it is effecti ve in killing cancer ce ll s, adriamycin has troublesome side effects. "It works we ll on cancer cell s, but it is extremely toxic to the heart," says Abram– son. "Over a period of time it causes severe deterioration of cardi ac muscle. We don 't know why it does thi s, but we do know that adriamyci n is effecti ve in releas ing calcium from the sarcoplasmic reticulum ." Recently, Abramson and hi s co llaborators have shown that very hi gh concentrations of caffe ine inh ibit the anti -cancer drug·s effect on the calcium release mechanism. "We're not talking about the amount of caffei ne we all think of in a cup of coffee," said Abramson. "We use huge doses in a highly controlled sc ientific environment. Work with this inhibitor and related compounds, says Abramson , may resu lt in decreasing the toxicity of adri amyc in thus providing a major contribution to cancer therapy and , from this PSU laboratory, advancing calc ium research worldwide. D PSU 11