Influence of aging and growth hormone on different members of the NFkB family and IkB expression in the heart from a murine model of senescence-accelerated aging

Exp Gerontol. 2016 Jan:73:114-20. doi: 10.1016/j.exger.2015.11.005. Epub 2015 Nov 12.

Abstract

Inflammation is related to several pathological processes. The aim of this study was to investigate the protein expression of the different subunits of the nuclear factor Kappa b (NFkBp65, p50, p105, p52, p100) and the protein expressions of IkB beta and alpha in the hearts from a murine model of accelerated aging (SAM model) by Western blot. In addition, the translocation of some isoforms of NFkB from cytosol to nuclei (NFkBp65, p50, p52) and ATP level content was studied. In addition we investigated the effect of the chronic administration of growth hormone (GH) on these age-related parameters. SAMP8 and SAMR1 mice of 2 and 10 months of age were used (n = 30). Animals were divided into five experimental groups: 2 old untreated (SAMP8/SAMR1), 2 young control (SAMP8/SAMR1) and one GH treated-old groups (SAMP8). Age-related changes were found in the studied parameters. We were able to see decreases of ATP level contents and the translocation of the nuclear factor kappa B p50, p52 and p65 from cytosol to nuclei in old SAMP8 mice together with a decrease of IKB proteins. However p100 and p105 did not show differences with aging. No significant changes were recorded in SAMR1 animals. GH treatment showed beneficial effects in old SAMP8 mice inducing an increase in ATP levels and inhibiting the translocation of some NFkB subunits such as p52. Our results supported the relation of NFkB activation with enhanced apoptosis and pro-inflammatory status in old SAMP8 mice and suggested a selective beneficial effect of the GH treatment, which was able to partially reduce the incidence of some deleterious changes in the heart of those mice.

Keywords: Aging; Apoptosis; Cardiovascular system; Growth hormone; Inflammation; NFkB; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Aging / drug effects
  • Aging / physiology
  • Aging, Premature / metabolism*
  • Aging, Premature / prevention & control
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cell Nucleus / metabolism
  • Cytosol / metabolism
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / methods
  • Growth Hormone / pharmacology*
  • Growth Hormone / therapeutic use
  • Heart / drug effects
  • I-kappa B Kinase / metabolism*
  • Male
  • Mice, Inbred Strains
  • Myocardium / metabolism*
  • NF-kappaB-Inducing Kinase
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Protein Isoforms / metabolism
  • Protein Serine-Threonine Kinases / metabolism*

Substances

  • Protein Isoforms
  • Adenosine Triphosphate
  • Growth Hormone
  • Protein Serine-Threonine Kinases
  • I-kappa B Kinase