Effect of aging on gastric mucosal defense mechanisms: ROS, apoptosis, angiogenesis, and sensory neurons

Kang JM, Kim N, Kim J, Oh E, Lee B, Lee BH, Shin CM, Park JH, Lee MK, Nam RH, Lee HE, Lee HS, Kim JS, Jung HC, Song IS. Effect of aging on gastric mucosal defense mechanisms: ROS, apoptosis, angiogenesis, and sensory neurons. Am J Physiol Gastrointest Liver Physiol 299: G1147-G1153, 2010. First published August 19, 2010; doi: 10.1152/ajpgi.00218.2010.-Aging changes in the stomach lead to a decreased capacity for tissue repair in response to gastric acid. The aim of this study was to determine the mechanism associated with the increased susceptibility to injury of aging mucosa including reactive oxygen species (5), apoptosis, angiogenesis, and sensory neuron activity. Fischer 344 rats at four different ages (6, 31, 74 wk, and 2 yr of age) were studied. The connective tissue indicators [salt-soluble collagen and sulfated glycosaminoglycan (sGAG)], lipid hydroperoxide (LPO), myeloperoxidase (MPO), and hexosamine were assessed. We also evaluated the expression of early growth response-1 (Egr-1), phosphatase and tension homologue deleted on chromosome 10 (PTEN), caspase-9 (index of apoptosis), VEGF (index of angiogenesis), calcitonin gene-related peptide (CGRP, index of sensory neurons), and neuronal nitric oxide synthase (nNOS). The histological connective tissue area in the lower part of rat gastric mucosa increased with aging, with increase of salt-soluble collagen and sGAG. LPO and MPO in old rats were significantly greater than in the young rats, whereas hexosamine was significantly reduced. The old gastric mucosa had increased expression of Egr-1, PTEN, and caspase-9, whereas the VEGF, CGRP, and nNOS expression were significantly reduced. These results indicate that the lower part of rat gastric mucosa was found to be replaced by connective tissue with accumulation of oxidative products with aging. In addition, impairment of apoptosis, angiogenesis, and sensory neuron activity via the activation of Egr-1 and PTEN might increase the susceptibility of gastric mucosa to injury during aging.This work was supported by grant no 06-2009-032 from the Seoul National University Bundang Hospital Research fund.Kang JM, 2010, J KOREAN MED SCI, V25, P875, DOI 10.3346/jkms.2010.25.6.875Abdel-Latif MMM, 2009, J CELL BIOCHEM, V108, P249, DOI 10.1002/jcb.22247Barros R, 2009, SCAND J GASTROENTERO, V44, P124, DOI 10.1080/00365520802530846KANG JM, 2009, DIG DIS SCI 0107Tarnawski A, 2007, GASTROENTEROLOGY, V133, P1938, DOI 10.1053/j.gastro.2007.08.037Holzer P, 2007, CURR OPIN PHARMACOL, V7, P563, DOI 10.1016/j.coph.2007.09.004Keates S, 2005, GUT, V54, P1363, DOI 10.1136/gut.2005.066977Sies H, 2005, J NUTR, V135, P969Salles N, 2005, EXP GERONTOL, V40, P353, DOI 10.1016/j.exger.2005.01.007Son TG, 2005, FREE RADICAL RES, V39, P283, DOI 10.1080/10715760500053461Abdel-Latif MMM, 2004, INFECT IMMUN, V72, P3549, DOI 10.1128/IAI.72.6.3547-3560.2004Yasui F, 2003, NEUROSCI LETT, V350, P66, DOI 10.1016/S0304-3940(03)00827-9MAJUMDAR AP, 2003, J PHYSL PHARM S4, V54, P143Thiel G, 2002, J CELL PHYSIOL, V193, P287, DOI 10.1002/jcp.10178Huang JH, 2002, J BIOL CHEM, V277, P10760, DOI 10.1074/jbc.M110219200Lenaz G, 2002, ANN NY ACAD SCI, V959, P199Virolle T, 2001, NAT CELL BIOL, V3, P1124Xiao ZQ, 2001, MECH AGEING DEV, V122, P1849Goto H, 2001, CLIN EXP PHARMACOL P, V28, P659Chung HY, 2001, ANN NY ACAD SCI, V928, P327Rivard A, 2000, J BIOL CHEM, V275, P29643Wallace JL, 2000, GASTROENTEROLOGY, V119, P512Ichikawa T, 2000, AM J PHYSIOL-GASTR L, V279, pG82Vogiagis D, 2000, AM J PHYSIOL-GASTR L, V278, pG820Atchison CR, 2000, DIGEST DIS SCI, V45, P614Matsugo S, 2000, NEUROSCI LETT, V278, P105Winterbourn CC, 2000, CURR OPIN HEMATOL, V7, P53Shian WM, 2000, SURG TODAY, V30, P49Cantley LC, 1999, P NATL ACAD SCI USA, V96, P4240Rivard A, 1999, CIRCULATION, V99, P111Wu XY, 1998, P NATL ACAD SCI USA, V95, P15587Liu L, 1998, AM J PHYSIOL-GASTR L, V275, pG943Stambolic V, 1998, CELL, V95, P29Holt PR, 1998, J GERONTOL A-BIOL, V53, pB168Holzer P, 1998, GASTROENTEROLOGY, V114, P823Aw TY, 1998, FREE RADICAL RES, V28, P637Mazure NM, 1997, BLOOD, V90, P3322Lee M, 1997, GUT, V41, P425McMahon SB, 1996, J LEUKOCYTE BIOL, V60, P159Miyake H, 1996, DIGEST DIS SCI, V41, P339Tokumaru S, 1996, MECH AGEING DEV, V86, P67LEE M, 1996, GERONTOLOGY, V42, P289RELAN NK, 1995, LAB INVEST, V73, P717GRONBECH JE, 1995, AM J PHYSIOL-GASTR L, V269, pG737LEE M, 1994, GASTROENTEROLOGY, V107, P1746FLIGIEL SEG, 1994, LAB INVEST, V70, P764GOTO H, 1992, BIOCHEM BIOPH RES CO, V186, P1443CRYER B, 1992, GASTROENTEROLOGY, V102, P1118MAJUMDAR APN, 1990, DIGEST DIS SCI, V35, P1364UCHIDA M, 1990, DIGEST DIS SCI, V35, P80HOLLANDER D, 1989, DIGEST DIS SCI, V34, P1692GEOKAS MC, 1985, CLIN GERIATR MED, V1, P177JAMES OFW, 1983, CLIN GASTROENTEROL, V12, P671NEUHAUS OW, 1957, ANAL CHEM, V29, P1230TARNAWSKI A, BIOCH BIOPHYS RES CO, V394, P291