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

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Abstract

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.

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Acknowledgment

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Ministry of Education (MOE)(2012R1A2A1A03670452), a grant of the Korea Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A111345), and supported by Kyungpook National University Research Fund, 2013.

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  1. Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Republic of Korea

    S. Park

  2. Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA

    K. W. Mathis

  3. Department of Internal Medicine, Kyungpook National University School of Medicine, Kyungpook National University, 50 Samduk-2Ga, Jung-Gu, Daegu, Republic of Korea, 700-721

    I. K. Lee

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Park, S., Mathis, K.W. & Lee, I.K. The physiological roles of apolipoprotein J/clusterin in metabolic and cardiovascular diseases. Rev Endocr Metab Disord 15, 45–53 (2014). https://doi.org/10.1007/s11154-013-9275-3

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