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A possible molecular explanation for pre-eclampsia
SCIENCE AND MEDICINE
A possible molecular explanation for pre-eclampsia disorder contained 9·4±1·5 nmol/mL. This difference was statistically significant and an even greater difference was observed between pre-eclampsia plasma and plasma samples taken from women
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
Decreased NO linked to pre-eclampsia
with normal pregnancies, and also non-pregnant women when S-nitrosothiol content was expressed per milligram of protein. Increased levels of S-nitrosothiols were almost completely accounted for by the increased concentrations of S-nitrosoalbumin. (Circulation Res 2001; 88: 1210–15.) “Since ascorbate is essential for the decomposition of S-nitrothiols to release NO, we speculate that the vitamin C deficiency that is usually associated with pre-eclampsia may result in less NO released from its protein-bound store in the blood”,
How P53 is activated following DNA damage
U
S investigators this week describe a mechanism that explains how the tumour suppressor gene P53 is activated. Activation of P53, which occurs in response to DNA damage, suppresses tumour growth by preventing abnormal cells from proliferating and by activating the apoptosis pathway. Under normal circumstances the activity of P53 is inhibited, and the researchers, led by Yue Xiong (Lineberger Comprehensive Cancer Center, University of North Carolina, NC, USA), discovered that the N-terminal region of P53 contains a nuclear export signal that is necessary for transporting P53 out of the nucleus and into the cytoplasm where it is degraded during normal cell growth (Science 2001; 292: 1910–15). “P53 should not function during normal cell growth under conditions of no DNA damage”,
THE LANCET • Vol 357 • June 9, 2001
explains Xiong. “So the cell exports P53 from the nucleus to the cytoplasm for degradation.” DNA damage triggers kinases that phosphorylate two serine residues at the N-terminal region of P53. “Phosphorylation of Ser-15 after DNA damage inhibits the function of this nuclear export signal, thereby blocking P53 export and its subsequent degradation in the cytoplasm”, says Xiong. As the wildtype P53 gene is still present in half of all tumours, these findings point to a new target for development of drugs to reactivate P53 in patients. “By blocking export of P53, one can imagine that one day we might be able to reactivate P53 function in tumours to either block cell proliferation or induce apoptosis”, Xiong comments.
Science Photo Library
re-eclampsia, a life-threatening complication of pregnancy that accounts for about 75 000 maternal deaths each year worldwide, could be caused by decreased availability of nitric oxide (NO), suggest US researchers this week. NO, which is one of the major mediators of blood vessel relaxation, is either used immediately after production, or is bound to albumin, forming S-nitrosoalbumin. “We have shown for the first time that women with pre-eclampsia have significantly higher levels of S-nitrosalbumin in their blood. This is consistent with the hypothesis that nitric oxide is being stored in the blood and is not being released in large enough quantities to maintain a healthy blood flow, leading to profound vasoconstriction throughout the woman’s body”, observes senior author Valerian Kagan (University of Pittsburgh, PA, USA). Vladimir Tyurin and colleagues obtained plasma samples from 21 pregnant women with pre-eclampsia and compared them with samples taken from 21 women at the same gestational stage of a normal pregnancy. Plasma from women who had pre-eclampsia contained 11·1±2·9 nmol/mL of total S-nitrosothiols whereas plasma from women with no symptoms of the
P
says co-author Carl Hubel, also of the University of Pittsburgh, PA, USA. Low levels of vitamin C may lead to decreased availability of NO in the general circulation and this might cause the vasoconstriction and vasospasm that are associated with the typical symptoms of pre-eclampsia—hypertension, proteinuria, and oedema, he explains. Currently, the only treatment for pre-eclampsia is early delivery of the fetus, so this condition accounts for a large proportion of premature births and a preventive treatment could save the lives of mothers and their babies. “Future clinical studies will be necessary to test whether antioxidant vitamins, particularly vitamin C, are able to reduce the incidence of preeclampsia by enhancing the release of NO from protein-bound reservoirs”, stresses Kagan. In the meantime, the group is also using transgenic rats that, like human beings, are unable to synthesise vitamin C and need to obtain it in their diet. “This animal model should provide further insight into NO–ascorbate interactions and their effects on artery function during pregnancy”, adds Kagan. Kathryn Senior
News in brief Heart muscle can grow back Heart muscle cells can regenerate after a myocardial infarction, a US study suggests. Expression of Ki67, a protein found in the nucleus of dividing heart muscle cells, was measured in myocytes from the hearts of 13 patients who had had heart attacks and in 10 controls. The number of myocytes multiplying in diseased hearts was greater than in normal hearts (N Engl J Med 2001; 344: 1750–57). Diabetics have excess mortality People with diabetes have a greater risk of death, regardless of age, sex, or affluence, say UK researchers. Compared with people without diabetes, life expectancy of patients diagnosed with diabetes before the age of 40 is reduced by 8 years. Even the most affluent had excess mortality (BMJ 2001; 322: 1389–93).
Helen Frankish
1857
For personal use. Only reproduce with permission from The Lancet Publishing Group.
A possible molecular explanation for pre-eclampsia disorder contained 9·4±1·5 nmol/mL. This difference was statistically significant and an even greater difference was observed between pre-eclampsia plasma and plasma samples taken from women
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
Decreased NO linked to pre-eclampsia
with normal pregnancies, and also non-pregnant women when S-nitrosothiol content was expressed per milligram of protein. Increased levels of S-nitrosothiols were almost completely accounted for by the increased concentrations of S-nitrosoalbumin. (Circulation Res 2001; 88: 1210–15.) “Since ascorbate is essential for the decomposition of S-nitrothiols to release NO, we speculate that the vitamin C deficiency that is usually associated with pre-eclampsia may result in less NO released from its protein-bound store in the blood”,
How P53 is activated following DNA damage
U
S investigators this week describe a mechanism that explains how the tumour suppressor gene P53 is activated. Activation of P53, which occurs in response to DNA damage, suppresses tumour growth by preventing abnormal cells from proliferating and by activating the apoptosis pathway. Under normal circumstances the activity of P53 is inhibited, and the researchers, led by Yue Xiong (Lineberger Comprehensive Cancer Center, University of North Carolina, NC, USA), discovered that the N-terminal region of P53 contains a nuclear export signal that is necessary for transporting P53 out of the nucleus and into the cytoplasm where it is degraded during normal cell growth (Science 2001; 292: 1910–15). “P53 should not function during normal cell growth under conditions of no DNA damage”,
THE LANCET • Vol 357 • June 9, 2001
explains Xiong. “So the cell exports P53 from the nucleus to the cytoplasm for degradation.” DNA damage triggers kinases that phosphorylate two serine residues at the N-terminal region of P53. “Phosphorylation of Ser-15 after DNA damage inhibits the function of this nuclear export signal, thereby blocking P53 export and its subsequent degradation in the cytoplasm”, says Xiong. As the wildtype P53 gene is still present in half of all tumours, these findings point to a new target for development of drugs to reactivate P53 in patients. “By blocking export of P53, one can imagine that one day we might be able to reactivate P53 function in tumours to either block cell proliferation or induce apoptosis”, Xiong comments.
Science Photo Library
re-eclampsia, a life-threatening complication of pregnancy that accounts for about 75 000 maternal deaths each year worldwide, could be caused by decreased availability of nitric oxide (NO), suggest US researchers this week. NO, which is one of the major mediators of blood vessel relaxation, is either used immediately after production, or is bound to albumin, forming S-nitrosoalbumin. “We have shown for the first time that women with pre-eclampsia have significantly higher levels of S-nitrosalbumin in their blood. This is consistent with the hypothesis that nitric oxide is being stored in the blood and is not being released in large enough quantities to maintain a healthy blood flow, leading to profound vasoconstriction throughout the woman’s body”, observes senior author Valerian Kagan (University of Pittsburgh, PA, USA). Vladimir Tyurin and colleagues obtained plasma samples from 21 pregnant women with pre-eclampsia and compared them with samples taken from 21 women at the same gestational stage of a normal pregnancy. Plasma from women who had pre-eclampsia contained 11·1±2·9 nmol/mL of total S-nitrosothiols whereas plasma from women with no symptoms of the
P
says co-author Carl Hubel, also of the University of Pittsburgh, PA, USA. Low levels of vitamin C may lead to decreased availability of NO in the general circulation and this might cause the vasoconstriction and vasospasm that are associated with the typical symptoms of pre-eclampsia—hypertension, proteinuria, and oedema, he explains. Currently, the only treatment for pre-eclampsia is early delivery of the fetus, so this condition accounts for a large proportion of premature births and a preventive treatment could save the lives of mothers and their babies. “Future clinical studies will be necessary to test whether antioxidant vitamins, particularly vitamin C, are able to reduce the incidence of preeclampsia by enhancing the release of NO from protein-bound reservoirs”, stresses Kagan. In the meantime, the group is also using transgenic rats that, like human beings, are unable to synthesise vitamin C and need to obtain it in their diet. “This animal model should provide further insight into NO–ascorbate interactions and their effects on artery function during pregnancy”, adds Kagan. Kathryn Senior
News in brief Heart muscle can grow back Heart muscle cells can regenerate after a myocardial infarction, a US study suggests. Expression of Ki67, a protein found in the nucleus of dividing heart muscle cells, was measured in myocytes from the hearts of 13 patients who had had heart attacks and in 10 controls. The number of myocytes multiplying in diseased hearts was greater than in normal hearts (N Engl J Med 2001; 344: 1750–57). Diabetics have excess mortality People with diabetes have a greater risk of death, regardless of age, sex, or affluence, say UK researchers. Compared with people without diabetes, life expectancy of patients diagnosed with diabetes before the age of 40 is reduced by 8 years. Even the most affluent had excess mortality (BMJ 2001; 322: 1389–93).
Helen Frankish
1857
For personal use. Only reproduce with permission from The Lancet Publishing Group.