title: Fluprostenol-induced MAPK signaling is independent of aging in Fischer 344/NNiaHSd x Brown Norway/BiNia rat aorta.
abstract: The factors that regulate vascular mechanotransduction and how this process may be altered with aging are poorly understood and have not been widely studied. Recent data suggest that increased tissue loading can result in the release of prostaglandin F2 alpha (PGF2alpha) and other reports indicate that aging diminishes the ability of the aged aorta to activate mitogen activated protein kinase (MAPK) signaling in response to increased loading. Using ex vivo incubations, here we investigate whether aging affects the ability of the aorta to induce phosphorylation of extracellular signal-regulated kinase 1/2 (ERK(1/2)-MAPK), p38-MAPK, and Jun N-terminal kinase (JNK-MAPK) activation following stimulation with a PGF2alpha analog, fluprostenol. Compared to aortas from 6-mo animals, the amounts of ERK(1/2)- and p38-MAPK remained unchanged with aging, while the level of JNK-MAPK protein increased by 135% and 100% at 30- and 36-mo, respectively. Aging increased the basal phosphorylation of ERK(1/2) (115% and 47%) and JNK (29% and 69%) (p <0.05) in 30- and 36-mo aortas, while p38 phosphorylation levels remained unaltered. Compared to age-matched controls, fluprostenol induced phosphorylation of ERK(1/2) (310%, 286%, and 554%), p38-MAPK (unchanged, 48%, and 148%), and JNK (78%, 88%, and 95%) in 6-, 30- and 36-mo aortas, respectively. These findings suggest that aging does not affect the ability of the rat aorta to activate ERK(1/2)-, p38-MAPK, and JNK-MAPK phosphorylation in response to PGF2alpha stimulation.
authors.affiliation: Department of Biological Sciences, Marshall University, Huntington, West Virginia 25755-1090, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Rice
authors.forename: Ernest M
authors.initials: EM
authors.lastname: Walker
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Kakarla
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Paturi
authors.forename: Miaozong
authors.initials: M
authors.lastname: Wu
authors.forename: Sumit
authors.initials: S
authors.lastname: Narula
authors.forename: Eric R
authors.initials: ER
authors.lastname: Blough
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015151:Immunoblotting; D008186:Luteolytic Agents / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D008186:Luteolytic Agents; D011461:Prostaglandins F, Synthetic; C006326:fluprostenol; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4