Targeting Nitric Oxide (NO) Deliveryin Vivo. Design of a Liver-Selective NO Donor Prodrug That Blocks Tumor Necrosis Factor-α-Induced Apoptosis and Toxicity in the Liver

1997 ◽  
Vol 40 (13) ◽  
pp. 1947-1954 ◽  
Author(s):  
Joseph E. Saavedra ◽  
Timothy R. Billiar ◽  
Debra L. Williams ◽  
Young-Myeong Kim ◽  
Simon C. Watkins ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
No Donor ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

Tumor necrosis factor-α plus actinomycin D-induced apoptosis of L929 cells is prevented by nitric oxide

Surgery Today ◽  
1999 ◽  
Vol 29 (10) ◽  
pp. 1059-1067 ◽  
Author(s):  
Shigeru Hakoda ◽  
Hiroyasu Ishikura ◽  
Naoshi Takeyama ◽  
Takaya Tanaka
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Actinomycin D ◽  
L929 Cells ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

Effects of Tumor Necrosis Factor-α and Nitric Oxide on Prostaglandins Secretion by the Bovine Oviduct Differ in the Isthmus and Ampulla and Depend on the Phase of the Estrous Cycle

2009 ◽  
Vol 234 (9) ◽  
pp. 1056-1066 ◽  
Author(s):  
Marta J. Siemieniuch ◽  
Izabela Woclawek-Potocka ◽  
Katarzyna Deptula ◽  
Kiyoshi Okuda ◽  
Dariusz J. Skarzynski
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis Factor ◽  
Estrous Cycle ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Positive Control ◽  
No Production ◽  
No Donor ◽  
Factor Α ◽  
Necrosis Factor

To determine the possible roles of tumor necrosis factor-α (TNFα) and nitric oxide (NO) in the bovine oviduct, ampulla and isthmus collected during the estrous cycle were exposed for 18 h to TNFα, NO donor (NONOate), NO synthase inhibitors (L-NOARG, L-NAME and AMT) and oxytocin (OT) as a positive control. Prostaglandins (PGs) and NO2/NO3 in conditioned media were measured. TNFα stimulated PGF2α secretion on Day 0 (onset of estrus = Day 0) and Days 2–3, in both the ampulla and isthmus, but on Days 18–20 only in ampulla. TNFα increased PGE2 secretion in both fragments in each phase. NONOate did not affect PGF2α secretion on Days 18–20, whereas this NO donor stimulated PGF2α secretion in both fragments on Day 0 and Days 2–3. TNFα increased NO2/NO3 production in every examined phase in the ampulla and on Days 2–3 in the isthmus. L-NAME lowered NO2/NO3 production regardless of phase or fragment. L-NOARG and AMT lowered NO2/NO3 production in both fragments on Day 0 and Days 2–3. The possible role of TNFα, NO or PGs on the oviductal contractility during the early-luteal phase was also examined. Neither TNFα nor NONOate influenced contractility in either fragment. Although PGF2α stimulated the contraction in both fragments, PGE2 decreased it. When taken together, TNFα seems to play some role as a modulator of PGF2α and PGE2 production and for transferring the embryo from the oviduct to the uterus by stimulating NO production in the bovine oviduct.

scholarly journals Estradiol Abrogates Apoptosis in Breast Cancer Cells through Inactivation of BAD: Ras-dependent Nongenomic Pathways Requiring Signaling through ERK and Akt

2004 ◽  
Vol 15 (7) ◽  
pp. 3266-3284 ◽  
Author(s):  
Romaine Ingrid Fernando ◽  
Jay Wimalasena
Keyword(s):  
Breast Cancer ◽  
Tumor Necrosis Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Dominant Negative ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

Estrogens such as 17-β estradiol (E2) play a critical role in sporadic breast cancer progression and decrease apoptosis in breast cancer cells. Our studies using estrogen receptor-positive MCF7 cells show that E2 abrogates apoptosis possibly through phosphorylation/inactivation of the proapoptotic protein BAD, which was rapidly phosphorylated at S112 and S136. Inhibition of BAD protein expression with specific antisense oligonucleotides reduced the effectiveness of tumor necrosis factor-α, H2O2, and serum starvation in causing apoptosis. Furthermore, the ability of E2 to prevent tumor necrosis factor-α-induced apoptosis was blocked by overexpression of the BAD S112A/S136A mutant but not the wild-type BAD. BAD S112A/S136A, which lacks phosphorylation sites for p90RSK1 and Akt, was not phosphorylated in response to E2 in vitro. E2 treatment rapidly activated phosphatidylinositol 3-kinase (PI-3K)/Akt and p90RSK1 to an extent similar to insulin-like growth factor-1 treatment. In agreement with p90RSK1 activation, E2 also rapidly activated extracellular signal-regulated kinase, and this activity was down-regulated by chemical and biological inhibition of PI-3K suggestive of cross talk between signaling pathways responding to E2. Dominant negative Ras blocked E2-induced BAD phosphorylation and the Raf-activator RasV12T35S induced BAD phosphorylation as well as enhanced E2-induced phosphorylation at S112. Chemical inhibition of PI-3K and mitogen-activated protein kinase kinase 1 inhibited E2-induced BAD phosphorylation at S112 and S136 and expression of dominant negative Ras-induced apoptosis in proliferating cells. Together, these data demonstrate a new nongenomic mechanism by which E2 prevents apoptosis.

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