Protein homeostasis in the aged and diseased heart

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Abstract

Protein homeostasis, the balance between protein synthesis and degradation, requires the clearance of misfolded and aggregated proteins and is therefore considered to be an essential aspect of establishing a physiologically effective proteome. Aging alters this balance, termed “proteostasis”, resulting in the progressive accumulation of misfolded and aggregated proteins. Defective proteostasis leads to the functional deterioration of diverse regulatory processes during aging and is implicated in the etiology of multiple pathological conditions underlying a variety of neurodegenerative diseases and in age-dependent cardiovascular disease. Detergent-insoluble protein aggregates have been reported by us in both aged and hypertensive hearts. The protein constituents were found to overlap with protein aggregates seen in neurodegenerative diseases such as Alzheimer’s disease. Therefore, targeting these protein components of aggregates may be a promising therapeutic strategy for cardiovascular pathologies associated with aging, ischemia, and/or hypertension.

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The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology.

Karen Bedard, Karl-Heinz Krause (2007)

For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the phagocyte NADPH oxidase itself (NOX2/gp91(phox)), the homologs are now referred to as the NOX family of NADPH oxidases. These enzymes share the capacity to transport electrons across the plasma membrane and to generate superoxide and other downstream reactive oxygen species (ROS). Activation mechanisms and tissue distribution of the different members of the family are markedly different. The physiological functions of NOX family enzymes include host defense, posttranlational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. NOX enzymes also contribute to a wide range of pathological processes. NOX deficiency may lead to immunosuppresion, lack of otoconogenesis, or hypothyroidism. Increased NOX activity also contributes to a large number or pathologies, in particular cardiovascular diseases and neurodegeneration. This review summarizes the current state of knowledge of the functions of NOX enzymes in physiology and pathology.

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Autophagy: cellular and molecular mechanisms.

Danielle Glick, Sandra Barth, Kay F Macleod (2010)

Autophagy is a self-degradative process that is important for balancing sources of energy at critical times in development and in response to nutrient stress. Autophagy also plays a housekeeping role in removing misfolded or aggregated proteins, clearing damaged organelles, such as mitochondria, endoplasmic reticulum and peroxisomes, as well as eliminating intracellular pathogens. Thus, autophagy is generally thought of as a survival mechanism, although its deregulation has been linked to non-apoptotic cell death. Autophagy can be either non-selective or selective in the removal of specific organelles, ribosomes and protein aggregates, although the mechanisms regulating aspects of selective autophagy are not fully worked out. In addition to elimination of intracellular aggregates and damaged organelles, autophagy promotes cellular senescence and cell surface antigen presentation, protects against genome instability and prevents necrosis, giving it a key role in preventing diseases such as cancer, neurodegeneration, cardiomyopathy, diabetes, liver disease, autoimmune diseases and infections. This review summarizes the most up-to-date findings on how autophagy is executed and regulated at the molecular level and how its disruption can lead to disease. Copyright (c) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Oxidative Stress: Harms and Benefits for Human Health

Gabriele Pizzino, Natasha Irrera, Mariapaola Cucinotta … (2017)

Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products. ROS can play, and in fact they do it, several physiological roles (i.e., cell signaling), and they are normally generated as by-products of oxygen metabolism; despite this, environmental stressors (i.e., UV, ionizing radiations, pollutants, and heavy metals) and xenobiotics (i.e., antiblastic drugs) contribute to greatly increase ROS production, therefore causing the imbalance that leads to cell and tissue damage (oxidative stress). Several antioxidants have been exploited in recent years for their actual or supposed beneficial effect against oxidative stress, such as vitamin E, flavonoids, and polyphenols. While we tend to describe oxidative stress just as harmful for human body, it is true as well that it is exploited as a therapeutic approach to treat clinical conditions such as cancer, with a certain degree of clinical success. In this review, we will describe the most recent findings in the oxidative stress field, highlighting both its bad and good sides for human health.

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Journal

Journal ID (nlm-journal-id): 101778645

Journal ID (pubmed-jr-id): 50607

Journal ID (nlm-ta): J Cardiovasc Aging

Journal ID (iso-abbrev): J Cardiovasc Aging

Title: The journal of cardiovascular aging

ISSN (Electronic): 2768-5993

Publication date Nihms-submitted: 24 March 2023

Publication date (Print): 2023

Publication date (Electronic): 7 March 2023

Publication date PMC-release: 21 April 2023

Volume: 3

Issue: 2

Electronic Location Identifier: 16

Affiliations

[1 ]Bioinformatics Program, University of Arkansas at Little Rock and University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

[2 ]Department of Geriatrics and Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

[3 ]Central Arkansas Veterans Healthcare Service, Little Rock, AR 72205, USA.

[4 ]Division of Cardiology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA.

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Authors’ contributions

Writing: Mainali N, Ayyadevara S

Additional contributions: Ganne A, Shmookler Reis RJ, Mehta JL

Correspondence to: Dr. Srinivas Ayyadevara, Reynolds Institute on Aging, 629 Jack Stephens Drive, Little Rock, AR 72205, USA. AyyadevaraSrinivas@ 123456uams.edu ; Dr. Robert J. Shmookler Reis, Reynolds Institute on Aging, 629 Jack Stephens Drive, Little Rock, AR 72205, USA. rjsr@ 123456uams.edu ; Dr. Jawahar L. Mehta, Department of Cardiology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA. mehtajl@ 123456uams.edu

Author information

Nirjal Mainali http://orcid.org/0000-0001-9679-1174

Srinivas Ayyadevara http://orcid.org/0000-0002-4572-6361

Akshatha Ganne http://orcid.org/0000-0003-4604-5194

Robert J. Shmookler Reis http://orcid.org/0000-0002-4691-0734

Jawahar L. Mehta http://orcid.org/0000-0003-0384-2097

Article

Manuscript ID: NIHMS1881766

DOI: 10.20517/jca.2023.4

PMC ID: 10121184

PubMed ID: 37092014

SO-VID: a147f8ad-f8ba-43e1-849d-7052defb9ea8

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This article is licensed under a Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Protein homeostasis in the aged and diseased heart

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Cardiovascular Innovations and Applications

Most cited references 169

The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology.

Autophagy: cellular and molecular mechanisms.

Oxidative Stress: Harms and Benefits for Human Health

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