東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Characterization of age-associated e...

Edwards, Michael G.

FindBook

Google Book

Amazon

博客來

Characterization of age-associated effects on the transcriptional response to oxidative stress in the mouse heart and skeletal muscle.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Characterization of age-associated effects on the transcriptional response to oxidative stress in the mouse heart and skeletal muscle./
作者:	Edwards, Michael G.
面頁冊數:	197 p.
附註:	Source: Dissertation Abstracts International, Volume: 66-05, Section: B, page: 2390.
Contained By:	Dissertation Abstracts International66-05B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3175450
ISBN:	0542139634

Characterization of age-associated effects on the transcriptional response to oxidative stress in the mouse heart and skeletal muscle.
Edwards, Michael G.

Characterization of age-associated effects on the transcriptional response to oxidative stress in the mouse heart and skeletal muscle. - 197 p.

Source: Dissertation Abstracts International, Volume: 66-05, Section: B, page: 2390.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2005.

The purpose of my graduate work was a global analysis of the effect of aging on the transcriptional response to stress. To accomplish this goal, high-density oligonucleotide arrays were used to quantify genome-scale differences in the transcriptional response to paraquat-induced oxidative stress in the heart and muscle of young and old mice. Results of this investigation revealed numerous examples of altered expression between young and old mice following oxidative insult in both tissue types. Among these was a reduction in the number of immediate early genes (IEGs) and growth arrest and DNA-damage inducible 45 (GADD45) gene families induced in older heart and muscle following paraquat treatment. Because these classes of genes are mediators or transcriptional targets of mitogen-activated protein kinase (MAPK) pathways, levels of active (phosphorylated) and total protein content of components of MAPK stress signaling were assayed in young and old skeletal muscle over the paraquat time course. It was found that constitutive levels of phospho-JNK, a critical signaling molecule for the MAPK c-Jun N-terminal protein kinase [JNK/stress-activated protein kinase (SAPK)] pathway, were elevated in old versus young skeletal muscle. Phospho-JNK levels increased almost immediately (1 hour post-paraquat treatment) in the young muscle following oxidative stress, whereas a delayed increase was observed in the older muscle over the same time period (5 hours post-paraquat treatment). In addition to the JNK-related findings, an age-related p53-mediated transcriptional program was identified in mouse skeletal muscle. The constitutive mRNA levels of genes induced by p53 was elevated in older muscle, while the levels for genes whose products have been shown to inhibit p53 activity were decreased with age. The age-related increase in p53 activity and expression of p53-related genes in mouse muscle as determined by DNA microarray analysis was also observed at the protein level as determined by Western blot (p53, p21 and GADD45a) and at the transcriptional level by RT-PCR (p21, GADD45a, p16, p53, bbc3, tnfrsf10b, pmaip1 and bok). These findings suggest that both p53 and JNK signaling are altered with age, and that this contributes to the transcriptional differences observed in the stress response of young and old mice.

ISBN: 0542139634Subjects--Topical Terms:

1017730
Biology, Genetics.

Characterization of age-associated effects on the transcriptional response to oxidative stress in the mouse heart and skeletal muscle.
LDR:03318nmm 2200289 4500 001 1819207
005 20061004161531.5
008 130610s2005 eng d
020 $a 0542139634
035 $a (UnM)AAI3175450
035 $a AAI3175450
040 $a UnM $c UnM
100 1 $a Edwards, Michael G. $3 1908504
245 1 0 $a Characterization of age-associated effects on the transcriptional response to oxidative stress in the mouse heart and skeletal muscle.
300 $a 197 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-05, Section: B, page: 2390.
500 $a Supervisor: Tomas A. Prolla.
502 $a Thesis (Ph.D.)--The University of Wisconsin - Madison, 2005.
520 $a The purpose of my graduate work was a global analysis of the effect of aging on the transcriptional response to stress. To accomplish this goal, high-density oligonucleotide arrays were used to quantify genome-scale differences in the transcriptional response to paraquat-induced oxidative stress in the heart and muscle of young and old mice. Results of this investigation revealed numerous examples of altered expression between young and old mice following oxidative insult in both tissue types. Among these was a reduction in the number of immediate early genes (IEGs) and growth arrest and DNA-damage inducible 45 (GADD45) gene families induced in older heart and muscle following paraquat treatment. Because these classes of genes are mediators or transcriptional targets of mitogen-activated protein kinase (MAPK) pathways, levels of active (phosphorylated) and total protein content of components of MAPK stress signaling were assayed in young and old skeletal muscle over the paraquat time course. It was found that constitutive levels of phospho-JNK, a critical signaling molecule for the MAPK c-Jun N-terminal protein kinase [JNK/stress-activated protein kinase (SAPK)] pathway, were elevated in old versus young skeletal muscle. Phospho-JNK levels increased almost immediately (1 hour post-paraquat treatment) in the young muscle following oxidative stress, whereas a delayed increase was observed in the older muscle over the same time period (5 hours post-paraquat treatment). In addition to the JNK-related findings, an age-related p53-mediated transcriptional program was identified in mouse skeletal muscle. The constitutive mRNA levels of genes induced by p53 was elevated in older muscle, while the levels for genes whose products have been shown to inhibit p53 activity were decreased with age. The age-related increase in p53 activity and expression of p53-related genes in mouse muscle as determined by DNA microarray analysis was also observed at the protein level as determined by Western blot (p53, p21 and GADD45a) and at the transcriptional level by RT-PCR (p21, GADD45a, p16, p53, bbc3, tnfrsf10b, pmaip1 and bok). These findings suggest that both p53 and JNK signaling are altered with age, and that this contributes to the transcriptional differences observed in the stress response of young and old mice.
590 $a School code: 0262.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Biology, Animal Physiology. $3 1017835
650 4 $a Biology, Molecular. $3 1017719
690 $a 0369
690 $a 0433
690 $a 0307
710 2 0 $a The University of Wisconsin - Madison. $3 626640
773 0 $t Dissertation Abstracts International $g 66-05B.
790 1 0 $a Prolla, Tomas A., $e advisor
790 $a 0262
791 $a Ph.D.
792 $a 2005
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3175450