title: Effect of growth hormone treatment on pancreatic inflammation, oxidative stress, and apoptosis related to aging in SAMP8 mice.
abstract: Aging is associated with an increase in inflammation, oxidative stress, and apoptosis. Furthermore, aging is accompanied by an alteration of the growth hormone (GH) -insulin-like growth factor-1 (IGF-1) axis. The aim of this study was to examine the regulation of these parameters in the pancreas of old mice and how GH treatment could affect this process. Male senescence-accelerated prone mice (SAMP8) and male senescence-accelerated resistant mice (SAMR1) 2 (young) and 10 months old were used (n = 40). Animals were divided into five experimental groups: 1 and 2, SAMP8/R1 young control; 3 and 4, SAMP8/R1 old control (untreated); and 5, SAMP8 old treated with GH. Physiologically equivalent doses of GH were administered for 1 month (2 mg subcutaneously [s.c.]/kg/day) and several parameters were analyzed. Aging was associated with increased inflammation, oxidative stress, and apoptosis (increased tumor necrosis factor-α [TNF-α], interleukin-β [IL-β], IL-6, monocyte chemoattractant protein-1 [MCP1], IL-2, heme oxygenase [HO-1], inducible nitric oxide synthase [iNOS], and nitric oxide metabolites [NOx]). The ratio of anti/pro apoptotic mRNA expression-B cell lymphoma 2 (Bcl-2) Bcl-2-associated X protein (BAX) + Bcl-xL/Bcl-2-associated death promoter (BAD)-was decreased during aging in SAMP8 mice. X-inhibitor of apoptosis (XIAP) was decreased during the aging process. Furthermore, no changes were observed in protein expression of nuclear factor-κB (NF-κB p65 and NF-κBp50-105. However, the protein expression of NF-κB p52-100 and inhibitor kappa B (IκB) alpha was increased with age in the pancreas of SAMP8 mice. On the other hand, the expression of IκB beta was decreased with aging. These results indicate that aging is associated with significant alterations in the relative expression of pancreatic genes involved in inflammation, oxidative stress, and apoptosis. According to our results, GH administration to old SAMP8 mice was able to improve pancreas from this parameters.
authors.affiliation: Department Physiology, Medical School, University Complutense of Madrid Medical School, University Complutense of Madrid, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Cuesta
authors.forename: Roman
authors.initials: R
authors.lastname: Kireev
authors.forename: Cruz
authors.initials: C
authors.lastname: García
authors.forename: Katherine
authors.initials: K
authors.lastname: Forman
authors.forename: Elena
authors.initials: E
authors.lastname: Vara
authors.forename: Jesús A F
authors.initials: JA
authors.lastname: Tresguerres
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D051636:X-Linked Inhibitor of Apoptosis Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D019382:Human Growth Hormone; D052247:Nitric Oxide Synthase Type II