How fat kills heart cells

March 27, 2001

Droplets of stored lipids accumulate in the cytoplasm of cardiac myocytes in a variety of cardiomyopathies, ranging from such chronic conditions as diabetes and obesity to the pathology that leads to sudden death in otherwise healthy young people. Still, it has been difficult to judge whether excess lipid storage reflects some other underlying pathology or whether it contributes directly to the death of heart muscle. Chiu and coworkers have tested this matter by forcing the overproduction of long-chain fatty acyl CoA in cardiac myocytes, using an enzyme that helps retain fatty acids in the cell following uptake. As a consequence of overexpressing the acyl-CoA synthetase (ACS1), long-chain fatty acids accumulate more rapidly than the cell can consume them or dispose of them, and they are stored in the form of triglycerides and other lipids. Chiu et al. show that ACS1 transgenic lines die prematurely, at a rate proportional to the level of enzyme overexpression. In these animals, cardiac myocytes die through apoptosis and necrosis, and those cells with with large lipid inclusions are lost preferentially. Interestingly, ceramide, a lipid mediator of apoptosis, is one of the species that accumulates in the hearts of these animals. While inhibition of ceramide signaling might therefore be protective, the authors note other quantitative and qualitative features of cellular lipids -- differences that could also contribute to the pathology seen in this model and, presumably, in humans with certain forms of cardiomyopathy.
-end-


JCI Journals

Related Enzyme Articles from Brightsurf:

Repairing the photosynthetic enzyme Rubisco
Researchers at the Max Planck Institute of Biochemistry decipher the molecular mechanism of Rubisco Activase

Oldest enzyme in cellular respiration isolated
Researchers from Goethe University have found what is perhaps the oldest enzyme in cellular respiration.

UQ researchers solve a 50-year-old enzyme mystery
Advanced herbicides and treatments for infection may result from the unravelling of a 50-year-old mystery by University of Queensland researchers.

Overactive enzyme causes hereditary hypertension
After more than 40 years, several teams at the MDC and ECRC have now made a breakthrough discovery with the help of two animal models: they have proven that an altered gene encoding the enzyme PDE3A causes an inherited form of high blood pressure.

Triggered by light, a novel way to switch on an enzyme
In living cells, enzymes drive biochemical metabolic processes. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics.

A 'corset' for the enzyme structure
The structure of enzymes determines how they control vital processes such as digestion or immune response.

Could inhibiting the DPP4 enzyme help treat coronavirus?
Researchers and clinicians are scrambling to find ways to combat COVID-19, including new therapeutics and eventually a vaccine.

Bacterial enzyme could become a new target for antibiotics
Scientists discover the structure of an enzyme, found in the human gut, that breaks down a component of collagen.

Chemists create new artificial enzyme
Rajeev Prabhakar, a computational chemist at the University of Miami, and his collaborators at the University of Michigan have created a novel, synthetic, three-stranded molecule that functions just like a natural metalloenzyme, or an enzyme that contains metal ions.

First artificial enzyme created with two non-biological groups
Scientists at the University of Groningen turned a non-enzymatic protein into a new, artificial enzyme by adding two abiological catalytic components: an unnatural amino acid and a catalytic copper complex.

Read More: Enzyme News and Enzyme Current Events
Brightsurf.com 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 Amazon.com.