Excessive Endoplasmic Reticulum Stress Correlates with Impaired Mitochondrial Dynamics, Mitophagy and Apoptosis, in Liver and Adipose Tissue, but Not in Muscles in EMS Horses

被引:57
作者
Marycz, Krzysztof [1 ,2 ]
Kornicka, Katarzyna [1 ]
Szlapka-Kosarzewska, Jolanta [1 ]
Weiss, Christine [3 ]
机构
[1] Wroclaw Univ Environm & Life Sci, Dept Expt Biol, PL-50375 Wroclaw, Poland
[2] Wroclaw Res Ctr EIT, Ul Stablowicka 147, PL-54066 Wroclaw, Poland
[3] PferdePraxis Dr Med Vet Daniel Weiss, Postmatte 14, CH-8807 Freienbach, Switzerland
关键词
metabolic syndrome; apoptosis; insulin resistance; mitochondria; autophagy; EQUINE METABOLIC SYNDROME; BINDING-PROTEIN; 4; INSULIN-RESISTANCE; OXIDATIVE STRESS; INFLAMMATORY RESPONSES; DIABETES-MELLITUS; GENE-EXPRESSION; OBESITY; FISSION; COMPLICATIONS;
D O I
10.3390/ijms19010165
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nowadays, endocrine disorders have become more frequent in both human and veterinary medicine. In horses, reduced physical activity combined with carbohydrate and sugar overload may result in the development of the so-called equine metabolic syndrome (EMS). EMS is characterized by insulin resistance, hyperinsulinemia, elevated blood triglyceride concentrations and usually obesity. Although the phenotypic features of EMS individuals are well known, the molecular mechanism underlying disease development remains elusive. Therefore, in the present study, we analyzed insulin-sensitive tissues, i.e., muscles, liver and adipose tissue in order to evaluate insulin resistance and apoptosis. Furthermore, we assessed mitochondrial dynamics and mitophagy in those tissues, because mitochondrial dysfunction is linked to the development of metabolic syndrome. We established the expression of genes related to insulin resistance, endoplasmic reticulum (ER) stress and mitochondria clearance by mitophagy using RT-PCR and Western blot. Cell ultrastructure was visualized using electron transmission microscopy. The results indicated that adipose tissue and liver of EMS horses were characterized by increased mitochondrial damage and mitophagy followed by triggering of apoptosis as mitophagy fails to restore cellular homeostasis. However, in muscles, apoptosis was reduced, suggesting the existence of a protective mechanism allowing that tissue to maintain homeostasis.
引用
收藏
页数:20
相关论文
共 39 条
  • [1] Endoplasmic Reticulum Stress and Type 2 Diabetes
    Back, Sung Hoon
    Kaufman, Randal J.
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, VOL 81, 2012, 81 : 767 - 793
  • [2] Modulating Mitochondrial Fission to Lower Diabetic Oxidative Stress
    Barazzoni, Rocco
    [J]. DIABETES, 2012, 61 (08) : 1915 - 1917
  • [3] Bardell AL, 2001, J PHARMACOL EXP THER, V296, P252
  • [4] Basinska K, 2015, J VET SCI, V16, P113, DOI [10.4142/jvs.2015.16.1.113, 10.4142/jvs.2015.16.1.107]
  • [5] Proinflammatory Cytokine and Chemokine Gene Expression Profiles in Subcutaneous and Visceral Adipose Tissue Depots of Insulin-Resistant and Insulin-Sensitive Light Breed Horses
    Burns, T. A.
    Geor, R. J.
    Mudge, M. C.
    McCutcheon, L. J.
    Hinchcliff, K. W.
    Belknap, J. K.
    [J]. JOURNAL OF VETERINARY INTERNAL MEDICINE, 2010, 24 (04): : 932 - 939
  • [6] Expression of S6K1 in human visceral adipose tissue is upregulated in obesity and related to insulin resistance and inflammation
    Catalan, Victoria
    Gomez-Ambrosi, Javier
    Rodriguez, Amaia
    Ramirez, Beatriz
    Andrada, Patricia
    Rotellar, Fernando
    Valenti, Victor
    Moncada, Rafael
    Marti, Pablo
    Silva, Camilo
    Salvador, Javier
    Fruehbeck, Gema
    [J]. ACTA DIABETOLOGICA, 2015, 52 (02) : 257 - 266
  • [7] Increased Unbound Retinol-binding Protein 4 Concentration Induces Apoptosis through Receptor-mediated Signaling
    Chen, Chao-Hung
    Hsieh, Tusty-Jiuan
    Lin, Kun-Der
    Lin, Hsing-Yi
    Lee, Mei-Yueh
    Hung, Wei-Wen
    Hsiao, Pi-Jung
    Shin, Shyi-Jang
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (13) : 9694 - 9707
  • [8] Endoplasmic reticulum stress, obesity and diabetes
    Cnop, Miriam
    Foufelle, Fabienne
    Velloso, Licio A.
    [J]. TRENDS IN MOLECULAR MEDICINE, 2012, 18 (01) : 59 - 68
  • [9] Autophagy: A Potential Link between Obesity and Insulin Resistance
    Codogno, Patrice
    Meijer, Alfred J.
    [J]. CELL METABOLISM, 2010, 11 (06) : 449 - 451
  • [10] Adipose tissue, adipokines, and inflammation
    Fantuzzi, G
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2005, 115 (05) : 911 - 919