Modulation of LPS-induced Cell Death by 5,6,7,8-Tetrahydrobiopterin

Pteridines ◽  
1999 ◽  
Vol 10 (4) ◽  
pp. 202-206
Author(s):  
Hiroyuki Iizuka ◽  
Hirofumi Sagara ◽  
Shuji Kojima
Keyword(s):  
Cell Death ◽  
Antioxidative Activity ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Nitrate Content ◽  
Oxygen Species ◽  
No Donor ◽  
Induced Apoptosis ◽  
Raw 264.7 Cell Line

SummaryIt has been previously reported that 5,6,7,S-tetrahydrobiopterin (BH4) modulates HL-60 cell death induced by a nitric oxide (NO) donor, S-nitroso-N-acetyl-D, L-penicillamine (SNAP). In this study, the role of endogenous BH4 was investigated in lipopolysaccharide (LPS)-induced apoptotic cell death. LPS induced an increase of DNA fragmentation and of nitrite and nitrate content (NOx content) in the macrophage- like RAW 264.7 cell line. 2,4-Diamino-6-hydroxypyrimidine (DAHP) , an inhibitor of BH4 synthesis, suppressed both of them. The NOx content of cells treated with LPS and interferon-y was much higher than that of cells treated with LPS alone. However, the degree of apoptotic cell death induced by LPS and interferon-y did not differ significantly from that induced by LPS alone. Further investigation revealed that LPS-induced cell death of RAW264.7 cells was mainly mediated by reactive oxygen species, such as hydrogen peroxide (H2O2). From these data, it was speculated that BH4 might be a modulator in NO-induced apoptosis, in which BH4 involves LPS-induced cell death by its function asa cofactor of inducible NO synthase and it suppresses the cell death mediated by NO and/or H2O2 via an antioxidative activity.

Proinflammatory phenotype of coronary arteries promotes endothelial apoptosis in aging

2004 ◽  
Vol 17 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Anna Csiszar ◽  
Zoltan Ungvari ◽  
Akos Koller ◽  
John G. Edwards ◽  
Gabor Kaley
Keyword(s):  
Cell Death ◽  
Coronary Arteries ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
The Elderly ◽  
Apoptotic Cell Death ◽  
Caspase 9 ◽  
No Donor ◽  
Endothelial Apoptosis ◽  
Age Related

Previously we demonstrated that aging in coronary arteries is associated with proinflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by enhancing endothelial apoptosis. To test this hypothesis we characterized proapoptotic alterations in the phenotype of coronary arteries of aged (26 mo old) and young (3 mo old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was an approximately fivefold increase in the number of apoptotic endothelial cells. In aged coronary arteries there was an increased expression of TNFα, TNFβ, and caspase 9 (microarray, real-time PCR), as well as increased caspase 9 and caspase 3 activity, whereas expression of TNFR1, TNFα-converting enzyme (TACE), Bcl-2, Bcl-X(L), Bid, Bax, caspase 8, and caspase 3 were unchanged. In vessel culture (18 h) incubation of aged coronary arteries with a TNF blocking antibody or the NO donor S-nitroso-penicillamine (SNAP) decreased apoptotic cell death. Incubation of young arteries with exogenous TNFα increased caspase 9 activity and elicited endothelial apoptosis, which was attenuated by SNAP. Inhibition of NO synthesis in cultured young coronary arteries also induced apoptotic cell death and potentiated the apoptotic effect of TNFα. Thus we propose that age-related upregulation of TNFα and caspase 9 and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to impaired endothelial function and ischemic heart disease in the elderly.

scholarly journals Isoflavones Isolated from the Seeds of Millettia ferruginea Induced Apoptotic Cell Death in Human Ovarian Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 207 ◽  
Author(s):  
Yi-Yue Wang ◽  
Jun Hyeok Kwak ◽  
Kyung-Tae Lee ◽  
Tsegaye Deyou ◽  
Young Pyo Jang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Millettia Ferruginea ◽  
Induced Apoptosis

The seeds of Millettia ferruginea are used in fishing, pesticides, and folk medicine in Ethiopia. Here, the anti-cancer effects of isoflavones isolated from M. ferruginea were evaluated in human ovarian cancer cells. We found that isoflavone ferrugone and 6,7-dimethoxy-3’,4’-methylenedioxy-8-(3,3-dimethylallyl)isoflavone (DMI) had potent cytotoxic effects on human ovarian cancer cell A2780 and SKOV3. Ferrugone and DMI treatment increased the sub-G1 cell population in a dose-dependent manner in A2780 cells. The cytotoxic activity of ferrugone and DMI was associated with the induction of apoptosis, as shown by an increase in annexin V-positive cells. Z-VAD-fmk, a broad-spectrum caspase inhibitor, and z-DEVD-fmk, a caspase-3 inhibitor, significantly reversed both the ferrugone and DMI-induced apoptosis, suggesting that cell death stimulated by the isoflavones is mediated by caspase-3-dependent apoptosis. Additionally, ferrugone-induced apoptosis was found to be caspase-8-dependent, while DMI-induced apoptosis was caspase-9-dependent. Notably, DMI, but not ferrugone, increased the intracellular levels of reactive oxygen species (ROS), and antioxidant N-acetyl-L-cysteine (NAC) attenuated the pro-apoptotic activity of DMI. These data suggest that DMI induced apoptotic cell death through the intrinsic pathway via ROS production, while ferrugone stimulated the extrinsic pathway in human ovarian cancer cells.

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