LabMedica

Download Mobile App
Recent News Expo Clinical Chem. Molecular Diagnostics Hematology Immunology Microbiology Pathology Technology Industry Focus

Macrophages Lacking Ubiquitin-Binding Protein Stimulate Growth of Atherosclerotic Plaques

By LabMedica International staff writers
Posted on 24 Jan 2016
Print article
Image: Cross-section of a mouse aorta with a large plaque. Red lines near the top of the cross-section are the wall of the aorta. The plaque contains a dysfunctional buildup of immune macrophages (pink) and protein waste (green) (Photo courtesy of Dr. I. Sergin, Washington University School of Medicine).
Image: Cross-section of a mouse aorta with a large plaque. Red lines near the top of the cross-section are the wall of the aorta. The plaque contains a dysfunctional buildup of immune macrophages (pink) and protein waste (green) (Photo courtesy of Dr. I. Sergin, Washington University School of Medicine).
In a mouse model of atherosclerosis it was shown that while lack of the autophagy chaperone protein p62 prevented ubiquinated dysfunctional proteins from being sequestered in vesicles in the cytoplasm of macrophages, the presence of these proteins in the cell contributed to increased macrophage infiltration into atherosclerotic plaques and exacerbated atherosclerosis.

The ubiquitin-binding protein p62 (sequestosome-1) is an autophagosome cargo protein that targets other proteins that bind to it for selective autophagy, a catabolic cellular mechanism that degrades dysfunctional proteins and organelles.

Investigators at the Washington University School of Medicine (St. Louis, MO, USA) worked with a mouse model that lacked the critical autophagy protein ATG5. They found that exposure of macrophages to lipids that promote atherosclerosis increased the abundance of the autophagy chaperone protein p62, and that p62 co-localized with ubiquitinated proteins in cytoplasmic inclusions, which were characterized by insoluble protein aggregates. The ATG5-null macrophages developed further p62 accumulation at the sites of large cytoplasmic ubiquitin-positive inclusion bodies.

The formation of the cytoplasmic inclusions depended on p62 because macrophages from a mouse atherosclerosis model that lacked p62, accumulated ubiquitinated proteins in a diffuse cytoplasmic pattern rather than in discrete vesicles. Mice that were p62-deficient formed greater numbers of more complex atherosclerotic plaques than control mice, and p62 deficiency further increased the atherosclerotic plaque burden in mice that lacked ATG5 in their macrophages.

"That p62 sequesters waste in brain cells was known, and its buildup is a marker for a dysfunctional waste-disposal system," said senior author Dr. Babak Razani, assistant professor of medicine at the Washington University School of Medicine. "But this is the first evidence that its function in macrophages is playing a role in atherosclerosis. If p62 is missing, the proteins do not aggregate. It is tempting to think this might be good for the cell, but we showed this is actually worse. It causes more damage than if the waste were corralled into a large "trash bin." You can imagine a situation where lots of trash is being generated and see that it would be better to keep it all in one place, rather than have it strewn across the floor. You might have difficulty removing the trash to the dumpster, but at least it is contained."

This study was published in the January 5, 2016, online edition of the journal Science Signaling.

Related Links:

Washington University School of Medicine


Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
Magnetic Bead Separation Modules
MAG and HEATMAG
POCT Fluorescent Immunoassay Analyzer
FIA Go
Gold Member
Systemic Autoimmune Testing Assay
BioPlex 2200 ANA Screen with MDSS

Print article

Channels

Clinical Chemistry

view channel
Image: The 3D printed miniature ionizer is a key component of a mass spectrometer (Photo courtesy of MIT)

3D Printed Point-Of-Care Mass Spectrometer Outperforms State-Of-The-Art Models

Mass spectrometry is a precise technique for identifying the chemical components of a sample and has significant potential for monitoring chronic illness health states, such as measuring hormone levels... Read more

Hematology

view channel
Image: The CAPILLARYS 3 DBS devices have received U.S. FDA 510(k) clearance (Photo courtesy of Sebia)

Next Generation Instrument Screens for Hemoglobin Disorders in Newborns

Hemoglobinopathies, the most widespread inherited conditions globally, affect about 7% of the population as carriers, with 2.7% of newborns being born with these conditions. The spectrum of clinical manifestations... Read more

Immunology

view channel
Image: The AI predictive model identifies the most potent cancer killing immune cells for use in immunotherapies (Photo courtesy of Shutterstock)

AI Predicts Tumor-Killing Cells with High Accuracy

Cellular immunotherapy involves extracting immune cells from a patient's tumor, potentially enhancing their cancer-fighting capabilities through engineering, and then expanding and reintroducing them into the body.... Read more

Microbiology

view channel
Image: The T-SPOT.TB test is now paired with the Auto-Pure 2400 liquid handling platform for accurate TB testing (Photo courtesy of Shutterstock)

Integrated Solution Ushers New Era of Automated Tuberculosis Testing

Tuberculosis (TB) is responsible for 1.3 million deaths every year, positioning it as one of the top killers globally due to a single infectious agent. In 2022, around 10.6 million people were diagnosed... Read more