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

Cell Physiol Biochem. 2017;41(1):41-54. doi: 10.1159/000455935. Epub 2017 Jan 17.

Abstract

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-1β, IL-6, and TNF-α), 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 IκB-α, 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 IκB-α 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.

Keywords: Apoptosis; Camel whey protein; Diabetes mellitus; Free radicals; Lymphocytes.

MeSH terms

  • Activating Transcription Factor 3 / metabolism*
  • Animals
  • Apoptosis / drug effects*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • Body Weight
  • Camelus / metabolism
  • Cytokines / blood
  • Cytokines / metabolism
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology*
  • Dietary Supplements
  • Enzyme-Linked Immunosorbent Assay
  • Immunohistochemistry
  • Insulin / metabolism
  • Male
  • Mice
  • NF-KappaB Inhibitor alpha / metabolism
  • Oxidative Stress / drug effects*
  • Phosphorylation / drug effects
  • Protective Agents / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Streptozocin / toxicity
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Thymus Gland / cytology
  • Up-Regulation / drug effects
  • Whey Proteins / pharmacology*

Substances

  • Activating Transcription Factor 3
  • Cytokines
  • Insulin
  • Protective Agents
  • Reactive Oxygen Species
  • Whey Proteins
  • NF-KappaB Inhibitor alpha
  • Streptozocin
  • Proto-Oncogene Proteins c-akt