Aging alters gastric mucosal responses to epidermal growth factor and transforming growth factor-alpha.
Aging alters gastric mucosal responses to epidermal growth factor and transforming growth factor-alpha.
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衰老改变胃粘膜对表皮生长因子和转化生长因子-α的反应。
DOI：
10.1152/ajpgi.2000.278.5.g805
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Majumdar,AP
中科院分区：
文献类型：
--
作者：
Turner,JR;Liu,L;Fligiel,SE;Jaszewski,R;Majumdar,AP
在年轻大鼠中给予药理学剂量的表皮生长因子（EGF）或转化生长因子-α（TGF-α）可刺激胃粘膜增殖，但在老年大鼠中，相同的治疗可抑制增殖。这可能是由于增强的配体诱导的EGF受体（EGFR）的内化。为了支持这一点，我们证明，虽然在年轻（4-6月龄）大鼠中单次注射EGF（10 μg/kg）或TGF-α（5 μg/kg）大大增加了膜相关EGFR酪氨酸激酶活性，但在老年（24月龄）大鼠中相同的治疗轻微抑制了酶活性。该处理还在老年大鼠的胃上皮中产生了更丰富的点状细胞质EGFR染色，与EGFR内化一致。体外分析表明，将老年大鼠而非年轻大鼠的分离胃粘膜细胞暴露于100 pM TGF-α导致细胞内EGFR酪氨酸激酶活性显著增加，老年大鼠粘膜中EGFR酪氨酸激酶活性的诱导剂量比年轻大鼠所需剂量低1，000倍。我们的数据表明，老化增强胃粘膜EGFR配体的敏感性。这可能部分解释了EGFR介导的抑制老年大鼠胃粘膜增殖的作用。
Administration of pharmacological doses of epidermal growth factor (EGF) or transforming growth factor-α (TGF-α) in young rats stimulates gastric mucosal proliferation, but, in aged rats, the same treatment inhibits proliferation. This may be due to enhanced ligand-induced internalization of EGF receptor (EGFR). In support of this, we demonstrated that although a single injection of EGF (10 μg/kg) or TGF-α (5 μg/kg) in young (4–6 mo old) rats greatly increased membrane-associated EGFR tyrosine kinase activity, the same treatment slightly inhibited the enzyme activity in aged (24 mo old) rats. This treatment also produced a greater abundance of punctate cytoplasmic EGFR staining in gastric epithelium of aged rats, consistent with EGFR internalization. In vitro analyses demonstrated that exposure of isolated gastric mucosal cells from aged but not young rats to 100 pM TGF-α resulted in marked increases in intracellular EGFR tyrosine kinase activity and that induction of EGFR tyrosine kinase activity in mucosal membranes from aged rats occurred at doses 1,000-fold less than those required in young rats. Our data suggest that aging enhances sensitivity of the gastric mucosa to EGFR ligands. This may partly explain EGFR-mediated inhibition of gastric mucosal proliferation in aged rats.
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大鼠衰老过程中胃粘膜酪氨酸激酶活性及其与细胞增殖的关系。
DOI：
10.1016/0304-4165(88)90043-8
发表时间：
1988
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Adhip P. Nandi Manjmdar;Adhip P. Nandi Manjmdar;Elizabeth A. Edgerton
通讯作者：
Elizabeth A. Edgerton
老年大鼠胃粘膜EGFR表达增加。
DOI：
10.1152/ajpgi.1997.273.2.g389
发表时间：
1997
期刊：
The American journal of physiology.
影响因子：
--
作者：
Tureaud,J;Sarkar,FH;Fligiel,SE;Kulkarni,S;Jaszewski,R;Reddy,K;Yu,Y;Majumdar,AP
通讯作者：
Majumdar,AP
影响因子：
13
作者：
Rusch, Valerie;Mendelsohn, John;Dmitrovsky, Ethan
通讯作者：
Dmitrovsky, Ethan
大鼠胃粘膜病变愈合过程中角质形成细胞和肝细胞生长因子基因的表达
影响因子：
29.4
作者：
Y. Kinoshita;H. Nakata;S. Hassan;M. Asahara;C. Kawanami;Y. Matsushima;Y. Naribayashi;C. Ping;D. Min;A. Nakamura
通讯作者：
A. Nakamura
CCK-B/胃泌素受体配体 CI-988 抑制胃泌素刺激的细胞增殖。
DOI：
10.1016/s0278-6915(98)00119-7
发表时间：
1999
期刊：
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
影响因子：
--
作者：
L. Dethloff;B. Barr;L. Bestervelt
通讯作者：
L. Bestervelt