Camel Whey Protein Protects B and T Cells from Apoptosis by Suppressing Activating Transcription Factor-3 (ATF-3)-Mediated Oxidative Stress and Enhancing Phosphorylation of AKT and IκB-α in Type I Diabetic Mice

被引:24
作者
Badr, Gamal [1 ,2 ]
Sayed, Leila H. [1 ,2 ,3 ]
Omar, Hossam El-Din M. [1 ,3 ]
Abd El-Rahim, Ali M. [4 ]
Ahmed, Emad A. [1 ,2 ]
Mahmoud, Mohamed H. [5 ,6 ]
机构
[1] Assiut Univ, Fac Sci, Zool Dept, Assiut 71516, Egypt
[2] Assiut Univ, Fac Sci, Zool Dept, Lab Immunol & Mol Physiol, Assiut, Egypt
[3] Assiut Univ, Fac Sci, Zool Dept, Lab Physiol, Assiut, Egypt
[4] Assiut Univ, Fac Agr, Dairy Dept, Assiut, Egypt
[5] King Saud Univ, Deanship Sci Res, Riyadh, Saudi Arabia
[6] Natl Res Ctr, Food Sci & Nutr Dept, Cairo, Egypt
关键词
Apoptosis; Camel whey protein; Diabetes mellitus; Free radicals; Lymphocytes; MILK-PROTEINS; SILICA NANOPARTICLES; BREAST-CANCER; GROWTH-FACTOR; MOUSE MODEL; BEE VENOM; LACTOFERRIN; PROLIFERATION; KINASE; VIRUS;
D O I
10.1159/000455935
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background: Diabetes mellitus (DM) is associated with severe immune system complications. Camel whey protein (CWP) decreases free radicals (ROS) and modulates immune functions, but its effect on DM-impaired immune systems has not been studied. We investigated the impact of CWP on the immune system in a Type 1 diabetes mouse model. Methods: Three experimental groups were used: (1) non-diabetic control; (2) diabetic; and (3) CWP-treated diabetic mice. Results: Induction of diabetes by streptozotocin was associated with reduction of body weight and insulin level, increase in glucose level and pro-inflammatory cytokines (IL-1 beta, IL-6, and TNF-alpha), and reduction in IL-2 and IL-4 levels. Upregulated ATF-3 expression was followed by a marked elevation in ROS levels. Lymphocytes from diabetic mice exhibited increased apoptosis through decreased phosphorylation of AKT and I kappa B-alpha, increased infiltration of T cells in the spleen and thymus, and decreased B cell numbers in the spleen. Supplementation with CWP decreased the levels of proinflammatory cytokines, ROS, and ATF-3 expression, and increased the levels of IL-4. Treatment with CWP decreased apoptosis by enhancing the phosphorylation of AKT and I kappa B-alpha. as well as T-cell and B-cell distribution in the spleen and thymus. Conclusions: Our findings suggest the beneficial effects of CWP supplementation during diabetes on decreasing and orchestrating the redox status and subsequently rescuing the immune cells from exhaustion. (C) 2017 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:41 / 54
页数:14
相关论文
共 64 条
[41]  
Khaskheli M., 2005, J AGR SOC SCI, V2, P164
[42]   Akt, a pleckstrin homology domain containing kinase, is activated primarily by phosphorylation [J].
Kohn, AD ;
Takeuchi, F ;
Roth, RA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (36) :21920-21926
[43]   The PI3K/Akt/mTOR signaling pathway mediates insulin-like growth factor 1-induced E-cadherin down-regulation and cell proliferation in ovarian cancer cells [J].
Lau, Man-Tat ;
Leung, Peter C. K. .
CANCER LETTERS, 2012, 326 (02) :191-198
[44]  
Legrand D, 2008, ADV EXP MED BIOL, V606, P163, DOI 10.1007/978-0-387-74087-4_6
[45]   Inhibitory effects of native and recombinant full-length camel lactoferrin and its N and C lobes on hepatitis C virus infection of Huh7.5 cells [J].
Liao, Yalin ;
El-Fakkarany, Esmail ;
Loennerdal, Bo ;
Redwan, Elrashdy M. .
JOURNAL OF MEDICAL MICROBIOLOGY, 2012, 61 (03) :375-383
[46]  
Longmire M., 2008, Nanomedicine, V3, P703
[47]  
MACHNICKI M, 1993, INT J EXP PATHOL, V74, P433
[48]   Numerical defects in CD8+CD28- T-suppressor lymphocyte population in patients with type 1 diabetes mellitus and multiple sclerosis [J].
Mikulkova, Zuzana ;
Praksova, Petra ;
Stourac, Pavel ;
Bednarik, Josef ;
Strajtova, Lucie ;
Pacasova, Rita ;
Belobradkova, Jana ;
Dite, Petr ;
Michalek, Jaroslav .
CELLULAR IMMUNOLOGY, 2010, 262 (02) :75-79
[49]  
Mohany M, 2012, J TOXICOL SCI, V37, P1
[50]   Advanced glycation end products-induced reactive oxygen species generation is partly through NF-kappa B activation in human aortic endothelial cells [J].
Morita, Miwa ;
Yano, Shozo ;
Yamaguchi, Toru ;
Sugimoto, Toshitsugu .
JOURNAL OF DIABETES AND ITS COMPLICATIONS, 2013, 27 (01) :11-15