The physiological roles of apolipoprotein J/clusterin in metabolic and cardiovascular diseases

Several isoforms of apolipoprotein J/clusterin (CLU) are encoded from a single gene located on chromosome 8 in humans. These isoforms are ubiquitously expressed in the tissues, and have been implicated in aging, neurodegenerative disorders, cancer progression, and metabolic/cardiovascular diseases i...

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Bibliographic Details
Published in:Reviews in endocrine & metabolic disorders 2014-03, Vol.15 (1), p.45-53
Main Authors: Park, S., Mathis, K. W., Lee, I. K.
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Cardiovascular Diseases - metabolism
Clusterin - metabolism
Diabetes
Endocrinology
Humans
Internal Medicine
Medicine
Medicine & Public Health
Metabolic Diseases - metabolism
Oxidative Stress - physiology
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Summary:Several isoforms of apolipoprotein J/clusterin (CLU) are encoded from a single gene located on chromosome 8 in humans. These isoforms are ubiquitously expressed in the tissues, and have been implicated in aging, neurodegenerative disorders, cancer progression, and metabolic/cardiovascular diseases including dyslipidemia, diabetes, atherosclerosis and myocardial infarction. The conventional secreted form of CLU (sCLU) is thought to be a component of high density lipoprotein-cholesterol. sCLU functions as a chaperone for misfolded proteins and it is thought to promote survival by reducing oxidative stress. Nuclear CLU, a truncated CLU formed by alternative splicing, is responsible for promoting apoptosis via a Bax-dependent pathway. There are putative regulatory sites in the promoter regions of CLU, which are occupied by transcription factors such as transforming growth factor (TGF)-β inhibitory element, activator protein-1, CLU-specific elements, and carbohydrate response element. However, the molecular mechanisms underlying the distinct roles of CLU in a variety of conditions remain unclear. Although the function of CLU in cancer or neurological disease has been studied intensively for three decades, physiological roles of CLU seem unexplored in the cardiovascular system and metabolic diseases. In this review, we will discuss general characteristics and regulations of CLU based on previous literature and assess the recent findings associated with its physiological roles in different tissues including the vasculature, heart, liver, kidney, adipose tissue, and brain.
ISSN:1389-9155
1573-2606
DOI:10.1007/s11154-013-9275-3