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

Role of NAD(P)H oxidase-derived hydr...

Guikema, Benjamin J.

FindBook

Google Book

Amazon

博客來

Role of NAD(P)H oxidase-derived hydrogen peroxide in regulating inducible nitric oxide synthase expression in interleukin-1beta-stimulated vascular smooth muscle.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Role of NAD(P)H oxidase-derived hydrogen peroxide in regulating inducible nitric oxide synthase expression in interleukin-1beta-stimulated vascular smooth muscle./
作者:	Guikema, Benjamin J.
面頁冊數:	164 p.
附註:	Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5765.
Contained By:	Dissertation Abstracts International66-11B.
標題:	Biology, Cell. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3195510
ISBN:	9780542408625

Role of NAD(P)H oxidase-derived hydrogen peroxide in regulating inducible nitric oxide synthase expression in interleukin-1beta-stimulated vascular smooth muscle.
Guikema, Benjamin J.

Role of NAD(P)H oxidase-derived hydrogen peroxide in regulating inducible nitric oxide synthase expression in interleukin-1beta-stimulated vascular smooth muscle. - 164 p.

Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5765.

Thesis (Ph.D.)--Albany Medical College of Union University, 2006.

Mounting evidence indicates that reactive oxygen species (ROS) produced in the vascular wall upon cytokine stimulation play an important regulatory function in cell signaling during vascular injury. This thesis tested the hypothesis that nonphagocytic NADPH oxidase (Nox)-derived H 2O2 regulates the expression of inducible nitric oxide synthase (iNOS) in primary rat vascular smooth muscle cells (VSMC) by modulating the activity of the mitogen activated protein kinases (MAPK). This is based on previous observations that IL-1beta-mediated iNOS expression in VSMC is completely dependent upon extracellular regulated kinases 1 and 2 (ERK1/2) activation. Using confoncal microscopy, we found that IL-1beta rapidly increased intracellular ROS production. Catalase loading inhibited ROS production and potentiated ERK activation and iNOS expression indicating that IL1beta-derived H2O2 negatively regulates iNOS expression through ERK1/2. Catalase loading had no effect on p38MAPK and inhibited activation of one isoform of c-Jun N-terminal kinase (JNK), however the effect of catalase on these MAPKs did not correlate with their role in regulating iNOS expression. Inhibition of p38MAPK potentiated while JNK inhibition partially inhibited iNOS expression. The non-phagocytic homologs of the NAD(P)H oxidase Nox1 and Nox4 were expressed in our VSMC, and Nox4 mRNA was approximately 1300 fold more abundant than Nox1 mRNA in quiescent VSMC. A 24 hour stimulation with IL-1beta caused a 500% increase in Nox1 mRNA and an 82% decrease in Nox4 mRNA levels. Silencing of Nox4 expression with adenoviral expression of siRNA hairpins prior to stimulation reduced IL-1beta induced ROS production and increased iNOS expression which is consistent with the effects of catalase. Nox1 siRNA had no effect on whole cell ROS production which is consistent with its low expression levels. However, silencing Nox1 potentiated iNOS expression indicating Nox1-derived ROS may play a role in cell signaling in spite of being too low to detect. All together, our results suggest that targeting intracellular oxidant producing enzymes in the injured vessel may increase the bioavailability of NO by increasing VSMC iNOS expression.

ISBN: 9780542408625Subjects--Topical Terms:

1017686
Biology, Cell.

Role of NAD(P)H oxidase-derived hydrogen peroxide in regulating inducible nitric oxide synthase expression in interleukin-1beta-stimulated vascular smooth muscle.
LDR:03208nmm 2200277 4500 001 1824120
005 20061128082942.5
008 130610s2006 eng d
020 $a 9780542408625
035 $a (UnM)AAI3195510
035 $a AAI3195510
040 $a UnM $c UnM
100 1 $a Guikema, Benjamin J. $3 1913211
245 1 0 $a Role of NAD(P)H oxidase-derived hydrogen peroxide in regulating inducible nitric oxide synthase expression in interleukin-1beta-stimulated vascular smooth muscle.
300 $a 164 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5765.
500 $a Adviser: David Jourd'heuil.
502 $a Thesis (Ph.D.)--Albany Medical College of Union University, 2006.
520 $a Mounting evidence indicates that reactive oxygen species (ROS) produced in the vascular wall upon cytokine stimulation play an important regulatory function in cell signaling during vascular injury. This thesis tested the hypothesis that nonphagocytic NADPH oxidase (Nox)-derived H 2O2 regulates the expression of inducible nitric oxide synthase (iNOS) in primary rat vascular smooth muscle cells (VSMC) by modulating the activity of the mitogen activated protein kinases (MAPK). This is based on previous observations that IL-1beta-mediated iNOS expression in VSMC is completely dependent upon extracellular regulated kinases 1 and 2 (ERK1/2) activation. Using confoncal microscopy, we found that IL-1beta rapidly increased intracellular ROS production. Catalase loading inhibited ROS production and potentiated ERK activation and iNOS expression indicating that IL1beta-derived H2O2 negatively regulates iNOS expression through ERK1/2. Catalase loading had no effect on p38MAPK and inhibited activation of one isoform of c-Jun N-terminal kinase (JNK), however the effect of catalase on these MAPKs did not correlate with their role in regulating iNOS expression. Inhibition of p38MAPK potentiated while JNK inhibition partially inhibited iNOS expression. The non-phagocytic homologs of the NAD(P)H oxidase Nox1 and Nox4 were expressed in our VSMC, and Nox4 mRNA was approximately 1300 fold more abundant than Nox1 mRNA in quiescent VSMC. A 24 hour stimulation with IL-1beta caused a 500% increase in Nox1 mRNA and an 82% decrease in Nox4 mRNA levels. Silencing of Nox4 expression with adenoviral expression of siRNA hairpins prior to stimulation reduced IL-1beta induced ROS production and increased iNOS expression which is consistent with the effects of catalase. Nox1 siRNA had no effect on whole cell ROS production which is consistent with its low expression levels. However, silencing Nox1 potentiated iNOS expression indicating Nox1-derived ROS may play a role in cell signaling in spite of being too low to detect. All together, our results suggest that targeting intracellular oxidant producing enzymes in the injured vessel may increase the bioavailability of NO by increasing VSMC iNOS expression.
590 $a School code: 0362.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Animal Physiology. $3 1017835
690 $a 0379
690 $a 0433
710 2 0 $a Albany Medical College of Union University. $3 1262873
773 0 $t Dissertation Abstracts International $g 66-11B.
790 1 0 $a Jourd'heuil, David, $e advisor
790 $a 0362
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3195510