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Cardiomyocyte protein trafficking: Relevance to heart disease and opportunities for therapeutic intervention.

ABSTRACT: Cardiomyocytes, the individual contractile units of heart muscle, are long-lived and robust. Given the longevity of these cells, it can be easy to overlook their dynamic intracellular environment that contain rapid protein movements and frequent protein turnover. Critical gene transcription and protein translation occur continuously, as well as trafficking and localization of proteins to specific functional zones of cell membrane. As heart failure becomes an increasingly important clinical entity, growing numbers of investigative teams are examining the cell biology of healthy and diseased cardiomyocytes. In this review, we introduce the major architectural structures and types of protein movements within cardiac cells, and then review recent studies that explore the regulation of such movements. We conclude by introducing current translational directions of the basic studies with a focus on novel areas of therapeutic development.

SUBMITTER: Xiao S

PROVIDER: S-EPMC4468031 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Cardiomyocyte protein trafficking: Relevance to heart disease and opportunities for therapeutic intervention.

Xiao Shaohua S Shaw Robin M RM

Trends in cardiovascular medicine 20141229 5

Cardiomyocytes, the individual contractile units of heart muscle, are long-lived and robust. Given the longevity of these cells, it can be easy to overlook their dynamic intracellular environment that contain rapid protein movements and frequent protein turnover. Critical gene transcription and protein translation occur continuously, as well as trafficking and localization of proteins to specific functional zones of cell membrane. As heart failure becomes an increasingly important clinical entit ...[more]

PMID: 25649302

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Project description:Mycobacterium tuberculosis causes chronic infection of mononuclear phagocytes, especially resident (alveolar) macrophages, recruited macrophages, and dendritic cells. Despite the importance of these cells in tuberculosis (TB) pathogenesis and immunity, little is known about the population dynamics of these cells at the sites of infection. We used a combination of congenic monocyte adoptive transfer, and pulse-chase labeling of DNA, to determine the kinetics and characteristics of trafficking, differentiation, and infection of mononuclear phagocytes during the chronic, adaptive immune phase of M. tuberculosis infection in mice. We found that Ly6Chi monocytes traffic rapidly to the lungs, where a subpopulation become Ly6Clo and remain in the lung vascular space, while the remainder migrate into the lung parenchyma and differentiate into Ly6Chi dendritic cells, CD11b+ dendritic cells, and recruited macrophages. As in humans with TB, M. tuberculosis-infected mice have increased numbers of blood monocytes; this is due to increased egress from the bone marrow, and not delayed egress from the blood. Pulse-chase labeling of dividing cells and flow cytometry analysis revealed a T1/2 of ~15 hrs for Ly6Chi monocytes, indicating that they differentiate rapidly upon entry to the parenchyma of infected lungs; in contrast, cells that differentiate from Ly6Chi monocytes turn over more slowly, but diminish in frequency in less than one week. New cells (identified by pulse-chase labeling) acquire bacteria within 1-3 days of appearance in the lungs, indicating that bacteria regularly encounter new cellular niches, even during the chronic stage of infection. Our findings that mononuclear phagocyte populations at the site of M. tuberculosis infection are highly dynamic provide support for specific approaches for host-directed therapies directed at monocytes, including trained immunity, as potential interventions in TB, by replacing cells with limited antimycobacterial capabilities with newly-recruited cells better able to restrict and kill M. tuberculosis.

Dataset Information

Cardiomyocyte protein trafficking: Relevance to heart disease and opportunities for therapeutic intervention.

Publications

Cardiomyocyte protein trafficking: Relevance to heart disease and opportunities for therapeutic intervention.

Similar Datasets

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