NEUROPROTECTIVE EFFECTS EXERTED BY 17β-ESTRADIOL (E2) AND THE INSULIN-LIKE GROWTH FACTOR IGF-I AFTER A FOCAL CEREBRAL ISCHEMIA IN THE ENDOTHELIN-1 RAT MODEL.

Abstract The cellular mechanisms involved in the accelerated bone loss occurring in association with estrogen deprivation as seen following the menopause are not fully understood. Insulin-like growth factor-I (IGF-I) is the local regulator of osteoblasts and one of its binding proteins, insulin-like growth factor-binding protein-4 (IGFBP-4), binds to IGF-I and suppresses biological activity. Previous studies have shown that the binding activity of IGFBP-4 in the conditioned medium of parathyroid hormone (PTH)-treated SaOS-2 osteoblastic-like cells is enhanced twofold and that this PTH-enhanced IGFBP-4 binding activity is abolished by 17β-estradiol. Levels of IGFBP-4 in the conditioned medium have been reported to be regulated not only at the level of production but also at the level of degradation which is catalyzed by a protease that specifically cleaves IGFBP-4. We have, therefore, studied the effects of 17β-estradiol and PTH on IGFBP-4 protease activity using SaOS-2 cells. SaOS-2 cells produce a protease that specifically cleaves IGFBP-4 into two fragments of approximately 18 and 14 kilodaltons. IGFBP-4 protease activity in the conditioned medium from PTH-treated cells was suppressed, while this PTH-induced suppression of protease activity was reversed by the addition of 17β-estradiol to the cultures. IGFBP-4 proteolytic activity was stimulated by IGF-I or IGF-II added exogenously and was inhibited by EDTA or protease inhibitors. IGFBP-4 proteolyzed in the conditioned medium from cells treated with PTH and 17β-estradiol was less effective at inhibiting IGF-I-stimulated [3H]thymidine incorporation into DNA compared with that proteolyzed in the conditioned medium from PTH-treated cells. The simplest explanation is that 17β-estradiol suppressed the inhibitory effect of PTH on osteoblastic activity by inhibiting the PTH-induced suppression of IGFBP-4 protease activity. Journal of Endocrinology (1996) 150, 223–229

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Delayed Neuroprotective Effect of Insulin-Like Growth Factor-I After Experimental Transient Focal Cerebral Ischemia Monitored With MRI

Stroke ◽

10.1161/01.str.32.5.1226 ◽

2001 ◽

Vol 32 (5) ◽

pp. 1226-1233 ◽

Cited By ~ 80

Author(s):

Wolf-R. Schäbitz ◽

Tobias T. Hoffmann ◽

Sabine Heiland ◽

Rainer Kollmar ◽

Jürgen Bardutzky ◽

...

Keyword(s):

Cerebral Ischemia ◽

Growth Factor ◽

Focal Cerebral Ischemia ◽

Neuroprotective Effect ◽

Insulin Like Growth Factor ◽

Factor I ◽

Transient Focal Cerebral Ischemia ◽

Growth Factor I

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In Vitro Changes in Secretion Activity of Rat Ovarian Fragments Induced by Molybdenum

Physiological Research ◽

10.33549/physiolres.932836 ◽

2014 ◽

pp. 807-809 ◽

Cited By ~ 2

Author(s):

S. ROYCHOUDHURY ◽

L. DETVANOVA ◽

A. V. SIROTKIN ◽

R. TOMAN ◽

A. KOLESAROVA

Keyword(s):

Growth Factor ◽

Ammonium Molybdate ◽

Insulin Like Growth Factor ◽

Factor I ◽

Study Results ◽

Igf I ◽

17Β Estradiol ◽

Growth Factor I ◽

Dose Dependent

The aim of this in vitro study was to examine the secretion activity (progesterone, 17β-estradiol and insulin-like growth factor-I) of rat ovarian fragments after molybdenum (Mo) addition. Rat ovarian fragments were incubated with ammonium molybdate (NH4)6Mo7O24.4H2O at the doses 90, 170, 330 and 500 µg.ml-1 for 24 h and compared with control group without Mo addition. Release of progesterone (P4), estradiol (17β-estradiol) and insulin-like growth factor I (IGF-I) by ovarian fragments was assessed by radioimmunoassay (RIA). Data show that P4 release by ovarian fragments was not affected by (NH4)6.Mo7O24.4H2O addition at all the doses used (90-500 µg.ml-1). However, addition of ammonium molybdate was found to cause a significant (P<0.05) dose-dependent decrease (at the doses 90, 170 and 500 µg.ml-1) in release of 17β-estradiol by ovarian fragments in comparison to control. Also, addition of ammonium molybdate significantly (P<0.05) inhibited IGF-I release at all the doses (90-500 µg.ml-1) used in the study. Results suggest ammonium molybdate induced inhibition in the release of growth factor IGF-I and its dose-dependent effect on secretion of steroid hormone 17β-estradiol but not progesterone. These data contribute to new insights regarding the mechanism of action of Mo on rat ovarian functions.

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Huperzine A exhibits anti-inflammatory and neuroprotective effects in a rat model of transient focal cerebral ischemia

Journal of Neurochemistry ◽

10.1111/j.1471-4159.2008.05504.x ◽

2008 ◽

Vol 106 (4) ◽

pp. 1594-1603 ◽

Cited By ~ 55

Author(s):

Zhi-Fei Wang ◽

Juan Wang ◽

Hai-Yan Zhang ◽

Xi-Can Tang

Keyword(s):

Cerebral Ischemia ◽

Rat Model ◽

Focal Cerebral Ischemia ◽

Huperzine A ◽

Neuroprotective Effects ◽

Transient Focal Cerebral Ischemia ◽

Anti Inflammatory

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Neuroprotective effects of pioglitazone in a rat model of permanent focal cerebral ischemia are associated with peroxisome proliferator-activated receptor gamma-mediated suppression of nuclear factor-κB signaling pathway

Neuroscience ◽

10.1016/j.neuroscience.2010.12.029 ◽

2011 ◽

Vol 176 ◽

pp. 381-395 ◽

Cited By ~ 49

Author(s):

H.-L. Zhang ◽

M. Xu ◽

C. Wei ◽

A.-P. Qin ◽

C.-F. Liu ◽

...

Keyword(s):

Cerebral Ischemia ◽

Signaling Pathway ◽

Rat Model ◽

Focal Cerebral Ischemia ◽

Nuclear Factor Κb ◽

Peroxisome Proliferator ◽

Nuclear Factor ◽

Neuroprotective Effects ◽

Peroxisome Proliferator Activated Receptor

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Neuroprotective Effects of a Novel Inhibitor of c-Jun N-Terminal Kinase in the Rat Model of Transient Focal Cerebral Ischemia

Cells ◽

10.3390/cells9081860 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1860 ◽

Cited By ~ 1

Author(s):

Mark B. Plotnikov ◽

Galina A. Chernysheva ◽

Vera I. Smolyakova ◽

Oleg I. Aliev ◽

Eugene S. Trofimova ◽

...

Keyword(s):

Cerebral Ischemia ◽

Infarct Size ◽

Rat Model ◽

Focal Cerebral Ischemia ◽

Neuroprotective Effect ◽

Specific Inhibitor ◽

Fold Increase ◽

Neuroprotective Activity ◽

Prophylactic Regimen ◽

Neuroprotective Effects

A novel specific inhibitor of c-Jun N-terminal kinase, 11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S), has a high affinity to JNK3 compared to JNK1/JNK2. The aim of this work was to study the mechanisms of neuroprotective activity of IQ-1S in the models of reversible focal cerebral ischemia (FCI) in Wistar rats. The animals were administered with an intraperitoneal injection of IQ-1S (5 and 25 mg/kg) or citicoline (500 mg/kg). Administration of IQ-1S exerted a pronounced dose-dependent neuroprotective effect, not inferior to the effects of citicoline. Administration of IQ-1S at doses of 5 and 25 mg/kg reduced the infarct size by 20% and 50%, respectively, 48 h after FCI, whereas administration of citicoline reduced the infarct size by 34%. The administration of IQ-1S was associated with a faster amelioration of neurological status. Control rats showed a 2.0-fold increase in phospho-c-Jun levels in the hippocampus compared to the corresponding values in sham-operated rats 4 h after FCI. Administration of IQ-1S at a dose of 25 mg/kg reduced JNK-dependent phosphorylation of c-Jun by 20%. Our findings suggest that IQ-1S inhibits JNK enzymatic activity in the hippocampus and protects against stroke injury when administered in the therapeutic and prophylactic regimen in the rat model of FCI.

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