Altered expression of iron regulatory proteins with aging is associated with transient hepatic iron accumulation after environmental heat stress.
Altered expression of iron regulatory proteins with aging is associated with transient hepatic iron accumulation after environmental heat stress.
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DOI：
10.1016/j.bcmd.2013.07.002
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发表时间：
2014-01
影响因子：
2.3
通讯作者：
Brown, Kyle E.
中科院分区：
文献类型：
--
作者：
Bloomer, Steven A.;Han, Okhee;Kregel, Kevin C.;Brown, Kyle E.
越来越多的证据表明，铁代谢的失调有助于与年龄相关的病理。我们以前观察到随着年龄的增长，肝脏铁增加，环境热应激刺激铁和氧化性肝损伤的老年大鼠进一步增加。本研究的目的是确定热应激后老年大鼠肝脏铁增加的机制。年轻（6个月）和老年（24个月）Fischer 344大鼠暴露于两次加热，间隔24 h。第二次热应激后收获肝脏，通过免疫印迹法测定铁输入蛋白转铁蛋白受体1（TFR1）和铁输出蛋白膜铁转运蛋白（Fpn）的蛋白水平。在非加热条件下，老年大鼠TFR1表达较低，Fpn表达较高。热应激后，老年大鼠的TFR1下降，铁螯合研究表明，这种下降依赖于高血压诱导的铁增加。热应激后幼鼠TFR1无明显变化。由于TFR1是由铁负调控，我们的研究结果表明，细胞内铁的增加与老化和热应激降低TFR1的表达。热应激后两个年龄组Fpn表达均增加，但老年大鼠的反应延迟。这种延迟诱导铁输出蛋白的机制表明，增加肝脏铁和氧化损伤后热应激在老年生物体。
An increasing body of evidence suggests that dysregulation of iron metabolism contributes to age-related pathologies. We have previously observed increased hepatic iron with aging, and that environmental heat stress stimulates a further increase in iron and oxidative liver injury in old rats. The purpose of this study was to determine a mechanism for the increase in hepatic iron in old rats after heat stress. Young (6 mo) and old (24 mo) Fischer 344 rats were exposed to two heating bouts separated by 24 h. Livers were harvested after the second heat stress, and protein levels of the iron import protein, transferrin receptor-1 (TFR1), and the iron export protein, ferroportin (Fpn) were determined by immunoblot. In the nonheated condition, old rats had lower TFR1 expression, and higher Fpn expression. After heat stress, TFR1 declined in the old rats, and iron chelation studies demonstrated that this decline was dependent on a hyperthermia-induced increase in iron. TFR1 did not change in the young rats after heat stress. Since TFR1 is inversely regulated by iron, our results suggest that the increase in intracellular iron with aging and heat stress lower TFR1 expression. Fpn expression increased in both age groups after heat stress, but this response was delayed in old rats. This delay in the induction of an iron exporter suggests a mechanism for the increase in hepatic iron and oxidative injury after heat stress in aged organisms.
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影响因子：
29
作者：
Donovan, A;Lima, CA;Andrews, NC
通讯作者：
Andrews, NC
影响因子：
20.3
作者：
Cohen, Lyora A.;Gutierrez, Lucia;Meyron-Holtz, Esther G.
通讯作者：
Meyron-Holtz, Esther G.
影响因子：
--
作者：
Argaud, Laurent;Ferry, Tristan;Robert, Dominique
通讯作者：
Robert, Dominique
DOI：
10.1152/ajpgi.1999.276.5.g1195
发表时间：
1999-05-01
影响因子：
4.5
作者：
Hall, DM;Baumgardner, KR;Gisolfi, CV
通讯作者：
Gisolfi, CV
影响因子：
20.3
作者：
Knutson, MD;Vafa, MR;Wessling-Resnick, M
通讯作者：
Wessling-Resnick, M