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Contact: Pat Pages
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American Society for Biochemistry and Molecular Biology

Story ideas from the Journal of Lipid Research

Articles published in the September 2007 issue of the Journal of Lipid Research (Vol. 48, No. 9)

ARTICLE HIGHLIGHTS


* Renal transplant recipients’ genetic makeup does not negatively impact fluvastatin use

Scientists report that when people with a transplanted kidney take fluvastatin, a drug against cardiovascular disease, their response to the drug is not influenced by their genetic composition.

People who receive a transplanted kidney are at risk of developing potentially fatal premature cardiovascular disease. One way to prevent this from happening is by taking fluvastatin, a drug that significantly reduces myocardial infarction and cardiac death. But patients’ genetic makeup has been reported to prevent similar cholesterol-lowering drugs, such as pravastatin, from working properly.

To examine potential effects of a genetic makeup on the efficacy of fluvastatin after patients receive a kidney transplant, Hallvard Holdaas and colleagues examined 42 genetic variations previously reported to affect fluvastatin metabolism, cholesterol regulation, cardiovascular disease, and the functioning of a transplanted kidney.

The scientists compared the effects of these genetic variations in 707 renal transplant patients who received fluvastatin and 697 patients who received a placebo and showed that the variations do not increase risks of developing a cardiovascular disease or a kidney disease. Consequently, statin therapy continues to be recommended to patients who received a transplanted kidney, regardless of their genetic makeup, the researchers concluded.

Article: “Genetic analysis of fluvastatin response and dyslipidemia in renal transplant recipients,” by Jonathan B. Singer, Hallvard Holdaas, Alan G. Jardine, Bengt Fellstrom, Ingrid Os, Georgina Bermann, and Joanne M. Meyer, on behalf of the Assessment of Lescol in Renal Transplantation (ALERT) Study Investigators

MEDIA CONTACT: Hallvard Holdaas, Medical Department, Rikshospitalet, Oslo, Norway; e-mail: Hallvard.Holdaas@rikshospitalet.no


* New skin-healing chemicals

Researchers have made synthetic lipids called pseudoceramides that are involved in skin cell growth and could be used in treating skin diseases in which skin cells grow abnormally.

Ceramides are lipids found in the outermost skin layer called the stratum corneum, which is made of dead skin cells and mainly serves as a physical barrier. Ceramides’ main biological function is to control how skin cells grow and differentiate – a process through which skin cells become specialized.

Scientists have created in the laboratory synthetic ceramides, called pseudoceramides, to treat skin diseases such as atopic dermatitis, a form of eczema characterized by red, flaky and very itchy skin; psoriasis, a disease that causes red scaly patches on the skin; and glucocorticoid-induced epidermal atrophy, in which the skin shrinks due to skin cell loss.

Jeung-Hoon Lee and colleagues have developed a new series of pseudoceramides and examined their effects on skin cells. They found that three pseudoceramides called K6PC-4, K6PC-5, and K6PC-9 significantly increased the amount of proteins produced when skin cells differentiate. These results were obtained both on cultured skin cells and on a reconstituted epidermis. K6PC-4, K6PC-5, and K6PC-9 may be used to treat skin diseases arising from abnormal growth of skin cells, the scientists concluded.

Article: “Novel synthetic ceramide derivatives increase intracellular calcium levels and promote epidermal keratinocyte differentiation,” by Yoo Bin Kwon, Chang Deok Kim, Jong-Kyung Youm, Hyung Sub Gwak, Byeong Deog Park, Seung Hun Lee, Saewha Jeon, Bo Joong Kim, Young-Joon Seo, Jang-Kyu Park, and Jeung-Hoon Lee

MEDIA CONTACT: Jeung-Hoon Lee, Chungnam National University, Daejeon, Korea; e-mail: jhoon@cnu.ac.kr


* New anti-inflammatory compound discovered

Scientists have discovered that a lipid known to protect the heart from inflammation and to cause skin allergic reactions also reduces inflammation of the kidneys. The discovery could help devise new ways of treating inflammatory kidney diseases.

The lipid, called sphingosylphosphorylcholine (SPC), has been shown to cause an increase in urine production in the kidneys and an abnormal accumulation of salt in the urine. But how SPC works in the kidneys is not completely understood.

Andrea Huwiler and colleagues examined the various proteins activated by SPC in kidney cells and showed for the first time that SPC triggers proteins known to reduce inflammation. Although more details will be needed to understand how these proteins and how SPC may interact with other anti-inflammatory proteins – such as transforming growth factor beta – SPC may be useful in the treatment of chronic inflammatory and fibrotic diseases of the kidneys, the scientists concluded.

Article: “Sphingosylphosphorylcholine acts in an anti-inflammatory manner in renal mesangial cells by reducing interleukin-1b-induced prostaglandin E2 formation,” by Cuiyan Xin, Shuyu Ren, Wolfgang Eberhardt, Josef Pfeilschifter, and Andrea Huwiler.

MEDIA CONTACT: Andrea Huwiler, University of Bern, Switzerland, and Wolfgang Goethe-Universitat, Frankfurt am Main, Germany; e-mail: huwiler@pki.unibe.ch


The following article is the fourth in a series of reviews on “adipocyte biology” or the biology of fat tissue. The other articles in the series will appear in future issues of the journal. All thematic review articles and can be accessed at: http://www.jlr.org/ (under “Thematic Reviews”).

* Understanding how obese fat cells work

In obese individuals, fat cells are bloated and inflamed because they receive too many nutrients, including lipids. In these cells, various components cannot work properly anymore and, instead, they activate new proteins to cope with the situation. One of the most challenged organelles in obese fat cells is a maze-like compartment called the endoplasmic reticulum (ER) that makes proteins and lipid droplets and senses the amount of nutrients that enter the cell.

Margaret F. Gregor and Gokhan S. Hotamisligil review current knowledge about how the ER works in fat cells and is modified in obesity. They show that when a fat cell receives too many nutrients, the ER is overwhelmed and triggers a process called the unfolded protein response (UPR). This process is one of many cellular responses that activate proteins that increase inflammation and can even result in the death of the cell. UPR also causes insulin resistance, a condition in which the production and function of insulin – a hormone produced by the pancreas – is impaired and blood sugar is too high.

The scientists show that by better understanding how the ER works, it may be possible to devise a therapy that enhances the function of the ER and maybe improve the health of obese people. Already, two molecules that protect the ER from obesity-related stress have shown some success in mice. Called PBA and TUDCA, the molecules decreased blood sugar and insulin levels and improved overall response to insulin production.

ER stress may also be reduced by targeting molecules involved in the UPR process. For example, a drug called Salubrinal was recently shown to inhibit one of the UPR-involved molecules and to protect cells from ER stress-induced cell death. Also, there is emerging evidence that anti-diabetic drugs may also work, at least in part, through this mechanism.

A deeper knowledge of how fat cells become dysfunctional will be critical in devising successful therapies in the future, the scientists conclude.

Article: “Adipocyte stress: the endoplasmic reticulum and metabolic disease,” by Margaret F. Gregor and Gokhan S. Hotamisligil

MEDIA CONTACT: Gokhan S. Hotamisligil, Harvard School of Public Health, Boston, Mass.; e-mail: ghotamis@hsph.harvard.edu

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The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society’s student members attend undergraduate or graduate institutions.

Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.

For more information about ASBMB, see the Society's Web site at www.asbmb.org.



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