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Recombinant HDL (Milano) protects endotoxin-challenged rats from multiple organ injury and dysfunction

  • Xinbo Zhang , Luya Wang and Baosheng Chen EMAIL logo
Published/Copyright: September 3, 2014
Biological Chemistry
From the journal Biological Chemistry Volume 396 Issue 1

Abstract

Endotoxemia, the systemic inflammatory host response to infection, leads to severe septic shock and multiple organ injury and dysfunction syndrome (MOPS), which cause mortality. Apolipoprotein A-IMilano (apoAIM), a naturally occurring cysteine mutant of apoAI with dimers as its effective form, showed an enhanced cardiovascular protective activity compared with wild-type apoAI (apoAIwt). To investigate the role of recombinant high-density lipoprotein (rHDL) reconstituted with apoAIM (rHDLM) on endotoxemia and MOPS, we examined the anti-inflammatory, anti-oxidant, and protective effects of this cysteine mutant against organ injury in endotoxin-challenged rat models compared with rHDLwt. In the present study, we demonstrated for the first time that pretreatment with rHDLM significantly attenuated liver and renal dysfunction and histopathological features of lung injury in endotoxin-challenged endotoxemia rats. Administration of rHDLM to endotoxemia rats dramatically suppressed proinflammatory cytokines and adhesion molecule increase in tumor necrosis factor α, interleukin 1β, interleukin 6, and intercellular adhesion molecule 1. In addition, rHDLM pretreatment inhibited lipid peroxidation and enhanced total antioxidant capacity in vivo. In comparison with rHDLwt, rHDLM showed enhanced capacity on anti-inflammatory and anti-oxidant functions. In summary, administration of rHDLM protected endotoxin-challenged endotoxemia and MOPS through enhanced anti-inflammatory and anti-oxidant properties.

Keywords: apolipoprotein A-I; cysteine mutant; endotoxemia; multiple organ dysfunction
Corresponding author: Baosheng Chen, National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Department of Biochemistry and Molecular Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China, e-mail:

Acknowledgments

This work was supported by a National Basic Research Grant 973 of China (2006)CB503801). The authors gratefully acknowledge the technical assistance and helpful suggestions of Hong Xue and Gang Wu.

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Supplemental Material

The online version of this article (DOI 10.1515/hsz-2014-0188) offers supplementary material, available to authorized users.

Received: 2014-4-19
Accepted: 2014-5-30
Published Online: 2014-9-3
Published in Print: 2015-1-1

©2014 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Cholesterol lowering: role in cancer prevention and treatment
  4. The role of the Mpv17 protein mutations of which cause mitochondrial DNA depletion syndrome (MDDS): lessons from homologs in different species
  5. Research Articles/Short Communications
  6. Genes and Nucleic Acids
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https://doi.org/10.1515/hsz-2014-0188
Keywords for this article
apolipoprotein A-I; cysteine mutant; endotoxemia; multiple organ dysfunction

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Cholesterol lowering: role in cancer prevention and treatment
  4. The role of the Mpv17 protein mutations of which cause mitochondrial DNA depletion syndrome (MDDS): lessons from homologs in different species
  5. Research Articles/Short Communications
  6. Genes and Nucleic Acids
  7. Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing
  8. Protein Structure and Function
  9. Complement activation by salivary agglutinin is secretor status dependent
  10. Synthesis, biological evaluation, and docking studies of PAR2-AP-derived pseudopeptides as inhibitors of kallikrein 5 and 6
  11. Membranes, Lipids, Glycobiology
  12. Recombinant HDL (Milano) protects endotoxin-challenged rats from multiple organ injury and dysfunction
  13. Cell Biology and Signaling
  14. miR-126 regulates platelet-derived growth factor receptor-α expression and migration of primary human osteoblasts
  15. Legumain expression, activity and secretion are increased during monocyte-to-macrophage differentiation and inhibited by atorvastatin
  16. Proteolysis
  17. Cell surface serine protease matriptase-2 suppresses fetuin-A/AHSG-mediated induction of hepcidin
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