Idun Pharmaceuticals Identifies Cell Type And Molecular Pathway Involved In Transplantation-Related Liver Damage

November 09, 1998

La Jolla, CA, November 9, 1998 - Idun Pharmaceuticals, Inc. today presented data on the cellular mechanism causing cell death during liver transplantation surgery at the American Association for the Study of Liver Diseases meeting in Chicago, IL. The research, titled "Selective Apoptosis of Sinusoidal Endothelial Cells Occurs During Ischemia/Reperfusion Injury of the Liver by a Caspase-Dependent Mechanism," was described in an oral presentation by Shiho Natori, M.D., of the Mayo Clinic in Rochester, MN and was co-authored by researchers at the Mayo Clinic and Idun.

In liver transplantation, the organ is temporarily deprived of oxygen while it is in transit between the donor and recipient. This deprivation is known as ischemia. Upon attachment to the recipient's circulatory system, blood and oxygen flow to the liver is re-established, a process known as reperfusion. While researchers have known that the ischemia/reperfusion, which occurs during transplantation, results in cell damage, the molecular pathway responsible for the damage had not been identified.

"Liver preservation injury is an important problem in transplantation surgery, but without a clear understanding of the mechanisms involved in the process we have not been able to prevent it or reduce its effects," said Karen Valentino, Ph.D., Director of Clinical Development at Idun and co-author on the paper. "These data show that liver ischemia/reperfusion injury induces a caspase-dependent apoptosis in endothelial cells. Now that we have identified which caspase is involved and which cell type is affected, we have the potential to develop therapies to intervene in the process and provide recipients with healthier livers."

Caspases are proteins that are known to play a role in programmed cell death (apoptosis). Researchers used a cell-based assay in combination with high-powered microscopy to detect apoptotic cells and to identify the type of affected cells in liver tissue sections. The assay, known as TUNEL, detects fragmented DNA, a hallmark of apoptosis. Transmission electron microscopy allows specific cell types to be identified visually. After determining that cell death resulted through an apoptotic pathway, scientists then added a compound known to inhibit caspase-3 in rat livers at various points of the liver preservation process. This compound, IDN-1965, is being developed by Idun. The data show that addition of IDN-1965 reduced apoptosis by 63 percent, as measured by the TUNEL assay.

"This research demonstrates that apoptosis plays a role in liver preservation injury and suggests that the process also may play an important role in ischemia/reperfusion damage in other organs and tissues as well," said Steven J. Mento, Ph.D., President and CEO of Idun. "We are very encouraged by the ability of IDN-1965 to reduce apoptosis-related cell death in liver transplantation injury and we will continue to evaluate the potential of this compound and other apoptosis-related compounds for treating a wide variety of diseases."

Idun Pharmaceuticals creates innovative human therapeutics with a primary focus on controlling apoptosis, or programmed cell death. In addition to its focus on small molecule inhibitors of apoptosis for applications in central nervous system disorders, cardiovascular disease, inflammation, and organ damage, Idun's drug discovery programs focus on small molecule activators of apoptosis for applications in cancer.
Editor's Note: This release is available on the Internet at Contact:
Steven J. Mento, Ph.D.
President and CEO Idun Pharmaceuticals, Inc.
(619) 623-1330 Noonan/Russo Communications, Inc.
Barbara Lindheim (investor)
(212) 696-4455, ext. 237
Amy Flood (media)
(415) 677-4455, ext. 211

Noonan/Russo Communications

Related Endothelial Cells Articles from Brightsurf:

JACC: BTS study looks at COVID-19's impact on cardiovascular tissue, endothelial cells
In the paper, ''Cardiorenal tissues express SARS-CoV-2 entry genes and basigin (BSG/CD147) increases with age in endothelial cells,'' publishing in JACC: Basic to Translational Research, researchers used publicly available gene expression data to determine the relative expression of key SARS-CoV-2 host entry/ processing genes in human cardiorenal tissues, including aorta, coronary artery, heart (atria and left ventricle), whole blood and the kidney and for comparison the colon, spleen and lung.

New way to target some rapidly dividing cancer cells, leaving healthy cells unharmed
Scientists at Johns Hopkins Medicine and the University of Oxford say they have found a new way to kill some multiplying human breast cancer cells by selectively attacking the core of their cell division machinery.

Nutrient deficiency in tumor cells attracts cells that suppress the immune system
A study led by IDIBELL researchers and published this week in the American journal PNAS shows that, by depriving tumor cells of glucose, they release a large number of signaling molecules.

Scientists modify CAR-T cells to target multiple sites on leukemia cells
In a preclinical study, scientists engineer new CAR-T cells to attack three sites on leukemia cells, instead of one.

Sphingotec's endothelial function biomarker bio-ADM® improves risk stratification of sepsis patients at ICUs
New study data show that monitoring blood levels of sphingotec's endothelial function biomarker bio-ADMĀ® on top of guideline parameter lactate improves risk stratification of sepsis patients admitted to intensive care units.

sphingotec's endothelial function biomarker bio-ADM® predicts need for organ support in general ICU patient population
Data from more than 2,000 patients enrolled in the FROG-ICU study demonstrate that high levels of bioactive adrenomedullin (bio-ADMĀ®) predict the need for organ support, ionotropes, and vasopressors in the general patient population at admission to the intensive care unit (ICU).

First-of-its-kind study in endothelial stem cells finds exposure to flavored e-cigarette liquids, e-cigarette use exacerbates cell dysfunction
There has been a rapid rise in e-cigarette use, but its health effects have not been well-studied and their effect on vascular health remains unknown.

Dead cells disrupt how immune cells respond to wounds and patrol for infection
Immune cells prioritise the clearance of dead cells overriding their normal migration to sites of injury.

Transplanted bone marrow endothelial progenitor cells delay ALS disease progression
Transplanting human bone marrow-derived endothelial progenitor cells into mice mimicking symptoms of amyotrophic lateral sclerosis (ALS) helped more motor neurons survive and slowed disease progression by repairing damage to the blood-spinal cord barrier, University of South Florida researchers report.

Revealed: How the 'Iron Man' of immune cells helps T cells fight infection
The immune system's killer T cells are crucial in fighting viral infections.

Read More: Endothelial Cells News and Endothelial Cells Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to