Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of the study was to investigate the involvement of angiotensin II receptor subtypes 1 and 2 in total interstitial cell and endothelial cell DNA synthesis and cardiac function after myocardial infarction (MI) in the rat. Rats with a MI were treated with either AT1 receptor antagonist GR138950C (2 mg/kg/day) or the AT2 receptor antagonist PD123319 (3 mg/kg/day). Total interstitial cell (that is endothelial cells and fibroblast-like cells) DNA synthesis in the interventricular septum was significantly increased 2 weeks after MI. 33+/-3% of DNA synthesizing cells were identified as endothelial cells. PD123319, but not GR138950C significantly reduced total interstitial DNA synthesis. Both agents did not alter the fraction of DNA synthesizing endothelial cells. The effects on cardiac function were studied in parallel groups. MI reduced both cardiac output and stroke volume at 3 weeks after MI PD123319 reduced CO, whereas GR138950C did not affect cardiac function. Thus, the data show that AT2 receptor blockade, but not AT1 receptor blockade early after rat myocardial infarction inhibits interstitial DNA synthesis and decreases cardiac function.
J Mol Cell Cardiol 1998 Feb
PMID:AT2 receptor blockade reduces cardiac interstitial cell DNA synthesis and cardiac function after rat myocardial infarction. 951 19

Myocardial infarctions and stroke arise primarily as a result of hypoxia/ischemia-induced cell injury. However, the molecular mechanism of cardiac cell death due to hypoxia has not been elucidated. We showed here that chemical hypoxia induced by 1 mM azide triggered apoptosis of isolated neonatal rat ventricular cardiac myocytes but had no effect on cardiac fibroblasts. The azide-induced cardiomyocyte apoptosis could be characterized by a reversible initiation phase (0-46 h after azide exposure) during which cytosolic ATP levels remained little affected. This was followed by an irreversible execution phase (12-18 h) exhibiting prominent internucleosomal DNA fragmentation, cell membrane leakage, mitochondrial dysfunction, and increased calpain messenger RNA. Blocking extracellular calcium influx or intracellular calcium release was each effective in suppressing myocyte apoptosis. Cell death was also found to be mediated by calcium sensitive signal transduction events based on the use of specific antagonists. Consistent with the induction of calpain expression during apoptosis, blocking de novo protein synthesis and calpain activity inhibited cell death. These regulatory features coupled with the ease of the cell system suggest that the myocyte apoptosis model described here should be useful in the study of events leading to the demise of the myocardium.
Mol Cell Biochem 1998 Jan
PMID:Chemical hypoxia triggers apoptosis of cultured neonatal rat cardiac myocytes: modulation by calcium-regulated proteases and protein kinases. 954 93

Despite epidemiological studies indicating a positive relationship between alcohol and stroke, little is known with regard to effect of chronic alcohol on neuronal injury after stroke. In this study, we examined the effect of chronic ethanol on mRNA levels of sarcoplasmic or endoplasmic Ca2+-ATPase (SERCA2b) and inositol 1,4, 5-triphosphate receptor (IP3R1) in gerbils subjected to global cerebral ischemia induced by ligation of both common carotid arteries. Gerbils were given daily by intragastric intubation either a liquid diet containing ethanol (4 g/kg) or the same diet with an isocaloric amount of sucrose for 35 days. They were subsequently subjected to a 5 min ischemic insult followed by reperfusion for 48 h. In agreement with other studies, ischemic insult caused significant decreases (P<0.05) in mRNA levels of both IP3R1 and SERCA2b in the hippocampal CA1 region but not in the dentate gyrus. Nevertheless, despite a significant (P<0.05) decrease in SERCA2b mRNA in the Purkinje neurons, chronic ethanol did not alter the expression of this mRNA species in the hippocampal CA1 neurons nor did it alter the decrease in SERCA2b mRNA due to cerebral ischemic insult. Since IP3R1 and SERCA2b are key mediators for regulation of intracellular Ca2+ stores, the decrease in SERCA2b mRNA but not IP3R1 mRNA in cerebellar neurons may be an important mechanism underlying alteration of calcium homeostasis and cerebellar degeneration upon chronic ethanol consumption.
Brain Res Mol Brain Res 1998 May
PMID:Changes in IP3R1 and SERCA2b mRNA levels in the gerbil brain after chronic ethanol administration and transient cerebral ischemia-reperfusion. 960 35

Changes in the orientation of the myosin regulatory light chain (RLC) in single muscle fibres were measured using polarised fluorescence from acetamidotetramethylrhodamine (ATR). Mutants of chicken skeletal RLC containing single cysteine residues at positions 2, 73, 94, 126 and 155 were labelled with either the 5 or 6-isomer of iodo-ATR, giving ten different probes. The labelled RLCs were exchanged into demembranated fibres from rabbit psoas muscle without significant effect on active force generation. Fluorescence polarisation measurements showed that nine out of the ten probe dipoles were more perpendicular to the fibre axis in the absence of ATP (in rigor) than in either relaxation or active contraction. The orientational distribution of the RLC region of the myosin head in active contraction is closer to the relaxed than to the rigor orientation, and is not equivalent to a linear combination of the relaxed and rigor orientations. Rapid length steps were applied to the fibres to synchronise the motions of myosin heads attached to actin. In active contraction the fluorescence polarisation changed both during the step, indicating elastic distortion of the RLC region of the myosin head, and during the subsequent rapid force recovery that is thought to signal the working stroke. The peak change in fluorescence polarisation produced by an active release of 5 nm per half sarcomere indicates an axial tilt of less than 5 degrees for all ten probes, if all the myosin heads in the fibre respond to the length step. This tilting was towards the rigor orientation for all ten probes, and could be explained by 14% of the heads moving to the rigor orientation. An active stretch tilted the heads away from the rigor conformation by a similar extent.
J Mol Biol 1998 Jun 05
PMID:Orientation changes of fluorescent probes at five sites on the myosin regulatory light chain during contraction of single skeletal muscle fibres. 964 45

It has been shown that docosahexaenoic acid (DHA) has numerous physiological actions. However, the precise mechanism of these actions is still obscure, and DHA is not yet regarded as a drug. The present study was undertaken to elucidate the effects of long-term administration of DHA on the serum lipid concentrations in stroke-prone spontaneously hypertensive rats (SPSHR). SPSHR was selected because serum lipid derangement is one of the primary risk factors in the development and maintenance of hypertension. DHA-treated SPSHR showed significantly lower blood pressure when compared with that of non-treated SPSHR; total cholesterol, triglyceride, low density lipoprotein and lipid peroxide levels were significantly decreased in DHA-treated SPSHR. On the other hand, the high density lipoprotein concentrations tended to increase in DHA-treated SPSHR when compared with those in non-treated SPSHR. These findings suggest that long-term administration of DHA has a protective effect against serum lipid derangement in SPSHR. This DHA-induced amelioration of serum lipid changes in SPSHR might be associated with mechanisms involving the antihypertensive action induced by DHA.
Res Commun Mol Pathol Pharmacol 1998 Apr
PMID:Ameliorative effects of docosahexaenoic acid on serum lipid changes in stroke-prone spontaneously hypertensive rats. 964 19

The gastric vascular architecture in stroke-prone spontaneously hypertensive rats (SHRSP) was studied three-dimensionally by vascular casting; controls were Wistar Kyoto rats (WKY). The vascular network of the gastric mucosa of WKY showed a cylindrical shape with regular morphology (honeycomb-like capillary network) along the vascular course. In contrast, in SHRSP, an irregular vascular network was formed, and arterioles in the gastric mucosa and serous membrane were difficult to detect. Aneurysms were also detected in some capillaries in SHRSP. We concluded that the development of hypertension may have caused the irregular capillary networks in the rat stomach.
Res Commun Mol Pathol Pharmacol 1998 Apr
PMID:Gastric vascular network in stroke-prone spontaneously hypertensive rats. 964 20

In malignant SHRSP (M-SHRSP), a strain of stroke-prone spontaneously hypertensive rat (SHRSP), blood pressure rapidly increases during early development (5 weeks of age). Changes in the gastric vascular architecture of WKY and M-SHRSP were investigated using scanning electron microscope images of vascular casts focusing on the morphological differences in the three-dimensional arrangement of the capillaries. In WKY, the density, tortuosity and regular honeycomb formation of the gastric vessels were studied. The casts of gastric capillaries were 5.9 +/- 0.6 microns in diameter with a regular smooth surface. In M-SHRSP, the overall vascular pattern was not regularly organized at 6.3 +/- 1.9 microns in capillary diameter. Administration of the Ca antagonist, manidipine, to 11-week-old M-SHRSP with hypertensive vascular lesions decreased blood pressure and prolonged the rats' survival. With the administration of manidipine, vascular morphological patterns became similar to that of normotensive WKY, and the mean capillary diameter was 8.4 +/- 1.2 microns. It seems that manidipine plays a role in the recovery of normal vascular structure, as well as decreasing blood pressure.
Res Commun Mol Pathol Pharmacol 1998 May
PMID:Changes in the gastric vascular network of malignant stroke-prone spontaneously hypertensive rats (M-SHRSP) after administration of the calcium antagonist manidipine. 966 69

Facilitated protein folding by the double toroidal bacterial chaperonin, GroEL/GroES, proceeds by a "two-stroke engine" mechanism in which an allosteric interaction between the two rings synchronizes the reaction cycle by controlling the binding and release of cochaperonin. Using chimeric chaperonin molecules assembled by fusing equatorial and apical domains derived from GroEL and its mammalian mitochondrial homolog, Hsp60, we show that productive folding by Hsp60 and its cognate cochaperonin, Hsp10, proceeds in vitro and in vivo without the formation of a two-ring structure. This simpler "one-stroke" engine works because Hsp60 has a different mechanism for the release of its cochaperonin cap and bound target protein.
Mol Cell 1998 Jul
PMID:A single ring is sufficient for productive chaperonin-mediated folding in vivo. 970 95

Transient neural injuries, such as asphyxia, can trigger considerable delayed neuronal death. Inappropriate induction of apoptosis is thought to play an important role in this process. Our studies have shown marked changes in the IGF system in the brain in response to these injuries with an induction of insulin growth factor (IGF)-1 and insulin growth factor binding protein (IGFBP)-2 and IGFBP-3 in glial cells in the region of injury. This suggests that the IGF-1 system may be an endogenous neuroprotective system. Earlier administration of IGF-1 - 2 h after injury reduced the phase of secondary neuronal loss suggesting that IGF-1 may well have therapeutic potential as a neuronal rescue agent. The action of IGF-1 appears to involve binding proteins, transport to the site of injury and the IGF-1 receptor and inhibition of apoptosis, but might also involve generation of GPE which itself appears to be neuroprotective. Together these results indicate considerable potential of these agents to treat stroke, perinatal asphyxia and other forms of acute brain injury.
Mol Cell Endocrinol 1998 May 25
PMID:Asphyxial brain injury--the role of the IGF system. 972 75

Increased blood viscosity facilitates the formation of thrombosis. This is an important risk factor in the occurrence of cerebral infarctions. The present study was undertaken to elucidate whether docosahexaenoic acid (DHA) inhibits blood viscosity, hematocrit and fibrinogen in the disease animal model, stroke-prone spontaneously hypertensive rats (SHRSP). An attempt was also made to clarify the effect of DHA on blood pressure in SHRSP. Blood viscosity, hematocrit and fibrinogen in non-treated SHRSP increased significantly when compared with levels in age-matched non-treated Wistar Kyoto rats (WKY). SHRSP rats which were administered DHA for 5 weeks displayed significant decreases in blood viscosity, hematocrit and fibrinogen when compared with the values in non-treated SHRSP. The blood pressure of DHA-treated SHRSP was significantly lower than that of non-treated SHRSP. A positive correlation existed between blood pressure and blood viscosity. These findings suggest that decreased blood viscosity induced by DHA appears to be associated with the reduction of thrombosis formation and hypotensive action in SHRSP.
Res Commun Mol Pathol Pharmacol 1998 Jun
PMID:Docosahexaenoic acid inhibits blood viscosity in stroke-prone spontaneously hypertensive rats. 973 13


<< Previous 1 2 3 4 5 6 7 8 9 10