In vitro myometrial response to aluminum fluoride in the pregnant rat following chronic hypoxia.

1996 ◽  
Vol 3 (2) ◽  
pp. 343A
Author(s):  
J RHEE
1996 ◽  
Vol 270 (3) ◽  
pp. E477-E482 ◽  
Author(s):  
J. W. Rhee ◽  
L. D. Longo ◽  
W. J. Pearce ◽  
N. H. Bae ◽  
G. J. Valenzuela ◽  
...  

Mechanisms involving the timing of normal parturition are not well understood in most animal species. To gain a greater understanding of the mechanisms, we employed hypoxia to perturb the normal system of parturition. The present study was designed to investigate the effects of chronic hypoxia on myometrial contractility in the near-term pregnant rat. Rats were exposed to room air (control) or to continuous hypoxia (10.5% O2) either from experimental days 19 through 21 (2-day exposure) or from experimental days 15 through 21 (6-day exposure). On day 21, blood was collected for hormone assays, and the uterine horns were collected from each dam. One horn was snap-frozen in liquid nitrogen for oxytocin (OT) receptor analysis, and the other was used for in vitro assessment of myometrial contractile responses to cumulative doses of OT or arginine vasopressin (AVP). Hypoxic exposure resulted in approximately 60% reduction of the maximal myometrial contractile response to OT and a significant reduction in OT binding sites from 256.9 +/- 34.9 to 84.9 +/- 21.3 fmol/mg protein (P<0.01). In contrast, the contractile response to AVP was unaffected after exposure to chronic hypoxia (P> 0.05). Additionally, we observed no difference in the plasma concentrations of estrogen, progesterone, and corticosterone. We conclude that chronic hypoxia decreased the effectiveness of OT-specific contractile mechanisms, at least partially through a decrease in OT binding sites.


2008 ◽  
Vol 88 (4) ◽  
pp. 198-203 ◽  
Author(s):  
Reena Sidhu ◽  
Manisha Singh ◽  
Gulfraz Samir ◽  
Ray J. Carson
Keyword(s):  

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 292
Author(s):  
Ada-Sophia Clees ◽  
Verena Stolp ◽  
Björn Häupl ◽  
Dominik C. Fuhrmann ◽  
Frank Wempe ◽  
...  

Multiple myeloma (MM) is the second most common hematologic malignancy, which is characterized by clonal proliferation of neoplastic plasma cells in the bone marrow. This microenvironment is characterized by low oxygen levels (1–6% O2), known as hypoxia. For MM cells, hypoxia is a physiologic feature that has been described to promote an aggressive phenotype and to confer drug resistance. However, studies on hypoxia are scarce and show little conformity. Here, we analyzed the mRNA expression of previously determined hypoxia markers to define the temporal adaptation of MM cells to chronic hypoxia. Subsequent analyses of the global proteome in MM cells and the stromal cell line HS-5 revealed hypoxia-dependent regulation of proteins, which directly or indirectly upregulate glycolysis. In addition, chronic hypoxia led to MM-specific regulation of nine distinct proteins. One of these proteins is the cysteine protease legumain (LGMN), the depletion of which led to a significant growth disadvantage of MM cell lines that is enhanced under hypoxia. Thus, herein, we report a methodologic strategy to examine MM cells under physiologic hypoxic conditions in vitro and to decipher and study previously masked hypoxia-specific therapeutic targets such as the cysteine protease LGMN.


1995 ◽  
Vol 108 (2) ◽  
pp. 789-796 ◽  
Author(s):  
C.B. Brewer ◽  
M.G. Roth

Protein phosphorylation and dephosphorylation systems modulate many cellular activities and have recently been implicated in the in vitro transport of newly synthesized proteins. Here we show that polarized transport from the Golgi to the plasma membrane in intact MDCK cells is regulated by phosphorylation-dephosphorylation. Transport is inhibited by the phosphatase inhibitor okadaic acid and is stimulated by the kinase inhibitor staurosporine. Stimulation of apical transport exceeds stimulation of basolateral transport by up to 5-fold. We also find that the G protein activator aluminum fluoride, which stimulates transport to the surface at low fluoride concentrations as previously reported, inhibits transport at higher concentrations. In the nonpolarized fibroblast cell line CV-1, neither staurosporine nor aluminum fluoride stimulates transport to the cell surface. Our results suggest that the phosphorylation-dephosphorylation system, like the G protein, may be involved in the specialized sorting process characteristic of polarized cells. We show some evidence that these two mechanisms of regulation may act through common intermediates.


1999 ◽  
Vol 276 (3) ◽  
pp. R799-R808 ◽  
Author(s):  
John Buchholz ◽  
Kim Edwards-Teunissen ◽  
Sue P. Duckles

To examine effects of development and chronic high-altitude hypoxia on sympathetic nerve function in sheep, norepinephrine release was measured in vitro from middle cerebral and facial arteries. Capsaicin was used to test the role of capsaicin-sensitive sensory nerves; norepinephrine release was not altered by capsaicin treatment. N ω-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO synthase, decreased stimulation-evoked norepinephrine release in middle cerebral arteries from normoxic sheep with no effect in hypoxic arteries or facial arteries. Thus NO-releasing nerves augmented norepinephrine release. Furthermore, the function of NO-releasing nerves declined after chronic hypoxia. Despite loss of the augmenting effects of NO, stimulation-evoked fractional norepinephrine release was unchanged after chronic hypoxia, suggesting that middle cerebral arteries adapt to hypoxia by increasing stimulation-evoked norepinephrine release. In fetal facial arteries, chronic hypoxia resulted in a decline in stimulation-evoked norepinephrine release, but there was an increase in the adult facial artery. In the adult, adaptation to chronic hypoxia is similar in both cerebral and facial arteries. However, differential adaptation in fetal adrenergic nerves may reflect differences in fetal redistribution of blood flow in the face of chronic hypoxia but could also possibly contribute to increased incidence of fetal morbidity.


1981 ◽  
Vol 25 (4) ◽  
pp. 683-691 ◽  
Author(s):  
Kazuyoshi Taya ◽  
Gilbert S. Greenwald

2015 ◽  
Vol 65 (6) ◽  
pp. 579-586 ◽  
Author(s):  
Cui-Ying Zheng ◽  
Li-Li Song ◽  
Jin-Kun Wen ◽  
Li-Min Li ◽  
Zong-Wei Guo ◽  
...  

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