[Two cases of pulmonary arteriovenous fistulas with Rendu-Osler-Weber disease].
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Adult↗
Biomedical subjects
A Nishiyama
Publications and source records attributed to A Nishiyama.
Effects of furosemide on the tubular reabsorption of nitrates in anesthetized dogs.
The present study was performed to determine the tubular sites of nitrite and nitrate (NO) reabsorption and the effects of furosemide on the renal handling of NOx in anesthetized dogs, using renal clearance and stop-flow methods. Furosemide (2 mg/kg, i.v.) increased the urinary excretion rates of Na+ (U(Na+)V) and NOx (U(NOx)V) with a reduction of tubular reabsorption rates of Na+ and NOx. During inhibition of renal nitric oxide (NO) synthesis by an intrarenal infusion of L-nitro arginine (30 microg/kg-min), furosemide also increased U(NOx)V and decreased tubular reabsorption rate of NOx from 96.5+/-0.8% to 86.6+/-1.7%. An intravenous infusion of 10% mannitol (0.5 ml/kg-min) also increased both U(Na+)V and U(NOx)V. In addition, after furosemide administration or mannitol infusion. U(NOx)V was correlated with U(Na+)V. In stop-flow experiments, the distal dip in NOx curve was observed and the site of the dip in NOx curve was identical to that of Na+ curve. Furosemide shifted upward the U/P(Na+)/U/P(Cr) and U/P(NOx)/U/P(Cr) at the distal dip, indicating inhibition of Na+ and NOx reabsorption at distal tubules. These results indicate that more than 96% of the filtered NOx is reabsorbed in the renal tubules, and that the tubular handling of NOx is very close to that of Na+. In addition, the stop-flow experiments demonstrate that furosemide inhibited the reabsorption of NOx as well as Na+ at the distal tubule.
Anesthesia↗
Comparative effects of fish oil given by gavage and fish oil-enriched diet on leukocytes.
The comparative effects of fish oil given by gavage and fish oil enriched diet on metabolism and function of lymphocytes and macrophages were investigated. For this purpose, the following parameters were examined: 1) phagocytosis capacity, production of superoxide (O2*-) and hydrogen peroxide (H2O2) by macrophages, 2) lymphocytes proliferation capacity, 3) antioxidant enzyme activities in the mesenteric lymph nodes (MEN) and liver, 4) Thiobarbituric Acid Reactive Substances (TBARS) content in MLN, liver, and plasma, 5) total antioxidant capacity of the plasma, and 6) fatty acid composition of macrophages, MLN, liver and plasma. Both FO treatments did not affect phagocytosis capacity but increased hydrogen peroxide production by macrophages in the presence of PMA. FO given by gavage markedly increased lymphocytes proliferation both in the absence (5.8-fold) and in the presence (16.7-fold) of Con A, whereas FO-rich diet showed an increase in the presence of Con A only (53.3%). FO given by gavage raised the proliferation index by 2.9-fold and FO-rich diet increased by 29% only as compared to controls. Concomitantly, FO given by gavage was more effective to increase TBARS content in plasma. The proportion of some fatty acids in the tissues and cells was also differently changed depending on the way FO was administered to rats: in particular: myristic, arachidonic, and eicosapentaenoic acids. This fact may partially explain the differences between both FO treatments.
Animals↗
Short- and long-term effects of amiodarone on the two components of cardiac delayed rectifier K(+) current.
BACKGROUND: Amiodarone is the most promising drug for the treatment of life-threatening tachyarrhythmias in patients with structural heart disease. The pharmacological effects of amiodarone on cardiac ion channels are complex and may differ for short-term and long-term administration. METHODS AND RESULTS: The delayed rectifier K(+) current (I(K)) of ventricular myocytes isolated from rabbit hearts was recorded with the whole-cell voltage-clamp technique. I(K) was separated into 2 components by use of specific blockers for either I(Ks) (chromanol 293B, 30 micromol/L) or I(Kr) (E-4031, 10 micromol/L). Short-term application of amiodarone caused a concentration-dependent decrease in I(Kr) with an IC(50) of 2.8 micromol/L (n=8) but only a minimal reduction in I(Ks). The short-term effects of amiodarone were also determined in Xenopus oocytes expressing the cloned human channels that conduct I(Kr) and I(Ks) (HERG and KvLQT1/minK). HERG current in oocytes was reduced by amiodarone (IC(50)=38 micromol/L), whereas KvLQT1/minK current was unaffected by 300 micromol/L amiodarone. To study the effects of long-term drug administration, rabbits were treated for 4 weeks with oral amiodarone (100 mg. kg(-1). d(-1)) before cell isolation. Long-term administration of amiodarone decreased I(K) to 55% (n=10) in control rabbits and altered the relative density of I(Kr) and I(Ks). The majority (92%) of current was I(Kr). mRNA levels of rabbit ERG,KVLQT1, and minK in left ventricular myocardium did not differ between control and long-term amiodarone. CONCLUSIONS: Amiodarone has differential effects on the 2 components of I(K), depending on the application period; short-term treatment inhibits primarily I(Kr), whereas long-term treatment reduces I(Ks).
Amiodarone↗
Transient expression of the NG2 proteoglycan by a subpopulation of activated macrophages in an excitotoxic hippocampal lesion.
Cells that express the NG2 proteoglycan (NG2+ cells) constitute a large glial population in the normal mature rodent brain. They can differentiate into oligodendrocytes but are distinct from mature oligodendrocytes, astrocytes, microglia, and neurons. Changes in NG2+ cells were examined in kainic acid-induced excitotoxic lesions of the hippocampus, and the relationship between NG2+ cells and reactive astrocytes and microglia was investigated between 1 and 90 days after lesioning. Two types of reactive NG2+ cells with altered morphology and increased NG2 immunoreactivity were observed in the lesion. Early changes, consisting of an increase in NG2 immunoreactivity and the number of processes, were apparent 24 h after lesioning and persisted through 3 months. These cells were distinct from reactive astrocytes or activated microglia/macrophages. A second type of reactive NG2+ cells appeared 2 weeks after injection, following an influx of macrophages. They had large, round cell bodies with short processes and expressed the microglia/macrophage antigens OX42 and ED1. Single cells coexpressing NG2 and macrophage/microglial antigens could be isolated from the lesion. The number of NG2+/OX42+ cells gradually declined and disappeared by 3 months after injection. They did not express glial fibrillary acidic protein or the alpha receptor for platelet-derived growth factor, indicating that they are distinct from astrocytes or oligodendrocyte progenitor cells. Cells that coexpressed NG2 and OX42 were never observed in hippocampal slice cultures treated with kainic acid, suggesting that NG2+/OX42+ cells are not derived from endogenous resident brain cells. These findings demonstrate that NG2 expression is transiently upregulated on activated macrophages/microglia that appear during the chronic stage in an excitotoxic lesion in the adult CNS.
Animals↗
Takayasu arteritis with multiple cardiovascular complications.
A 60-year-old Japanese woman first presented in 1990 with effort angina. She underwent coronary angiography and was diagnosed with bilateral coronary ostial stenosis and Takayasu arteritis. Coronary artery bypass graft surgery (CABG) for multiple vessels was attempted, but the blood flow in the bilateral internal thoracic and gastroepiploic arteries was to poor for a donor artery, and the calcification of the ascending aortic wall was too severe for anastomosis of saphenous vein grafts. Therefore, the proper hepatic artery was connected to the left anterior descending artery using a vein graft. In April 2000, the patient's angina worsened. Occlusions of both subclavian arteries, bilateral coronary ostial stenosis and vein graft occlusion, aortic valve regurgitation, and two severe stenoses of the descending aorta were observed. Aortic valve replacement, and coronary and aorta revascularization were desirable, but the severe aortic wall calcification and thickening rendered these interventions impossible. Treatment with medication was chosen. The patient was discharged without severe angina. A combination of these serious cardiovascular complications which do not allow any surgical intervention is very rare.
Aortic Valve Stenosis↗
A radiologic analysis of dentigerous cysts and odontogenic keratocysts associated with a mandibular third molar.
OBJECTIVE: The purpose of this study was to discriminate radiographically between dentigerous cysts (DCs) and odontogenic keratocysts (OKCs) associated with a mandibular third molar. STUDY DESIGN: The material consisted of panoramic radiographs of dentigerous cysts (44 patients, 45 cysts) and odontogenic keratocysts (15 patients, 16 cysts), all of which were related to a mandibular third molar. The radiographic images were analyzed with reference to the patients' ages and symptoms. RESULTS: The mean age of patients in the OKC group was less than that of patients in the DC group. The mean area of the cysts in the OKC group was larger than that of those in the DC group. The mean distance from the second to the third molar in the DC group was greater than that in the OKC group. Although there was a significant correlation between the area and distance in the DC and OKC groups, the patients' ages did not significantly correlate to the area and distance of either cyst. CONCLUSIONS: The OKCs had a tendency toward rapid growth in the patient's youth but short movement of a third molar compared with the DCs. The DCs and OKCs do not appear to develop gradually from the period when follicles or dental lamina were formed but arise at various periods randomly.
Adolescent↗
Redox regulation by thioredoxin and thioredoxin-binding proteins.
Recent works have shown the importance of reduction/oxidation (redox) regulation in various biological phenomena. Thioredoxin is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys- and constitutes a major thiol reducing system, the thioredoxin system. Thioredoxin plays multiple roles in cellular processes such as proliferation or apoptosis. It also promotes DNA binding of transcription factors such as NF-kappaB, AP-1, p53, and PEBP2. Overexpression of thioredoxin suppresses the degradation of IkappaB and the transactivation of NF-kappaB, whereas overexpression of nuclear-targeted thioredoxin exhibits the enhancement of NF-kappaB-dependent transactivation. ASK1, a MAP kinase kinase kinase mediating the TNF-alpha signal has been identified as a thioredoxin binding protein. Thioredoxin shows an inhibitory effect on the TNF-alpha induced activation of ASK1 and p38 MAP kinase pathway. We identified p40phox as the thioredoxin binding protein-1 (TBP-1) and vitamin D3 up-regulated protein 1 (VDUP1) as the thioredoxin binding protein-2 (TBP-2) by yeast two-hybrid system. TBP-2/VDUP1 negatively regulates the expression and reducing activity of thioredoxin. Thioredoxin interacting proteins may be involved in thioredoxin-mediating redox regulation.
Animals↗
Possible role of uncoupling protein in regulation of myocardial energy metabolism in aortic regurgitation model rats.
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Adenosine Triphosphate↗
Altered K(+) channel gene expression in diabetic rat ventricle: isoform switching between Kv4.2 and Kv1.4.
Expression of voltage-gated K(+) channels encoding the K(+) independent transient outward current in the streptozocin-induced diabetic (DM) rat ventricle was studied to determine the basis for slowed cardiac repolarization in diabetes mellitus. Although hypertrophy was not detected in diabetic rats at 12 wk after streptozocin treatment, ventricular Kv4.2 mRNA levels decreased 41% relative to nondiabetic controls. Kv1.4 mRNA levels increased 179% relative to controls, whereas Kv4.3 mRNA levels were unaffected. Immunohistochemistry and Western blot analysis of the diabetic heart showed that the density of the Kv4.2 protein decreased, whereas Kv1.4 protein increased. Thus isoform switching from Kv4.2 to Kv1.4 is most likely the mechanism underlying the slower kinetics of transient outward K(+) current observed in the diabetic ventricle. Brain Kv1.4, Kv4.2, or Kv4.3 mRNA levels were unaffected by diabetes. Myosin heavy chain (MHC) gene expression was altered with a 32% decrease in alpha-MHC mRNA and a 259% increase in beta-MHC mRNA levels in diabetic ventricle. Low-dose insulin-like growth factor-II (IGF-II) treatment during the last 6 of the 12 wk of diabetes (DM + IGF) protected against these changes in MHC mRNAs despite continued hyperglycemia and body weight loss. IGF-II treatment did not change K(+) channel mRNA levels in DM or control rat ventricles. Thus IGF treatment may prevent some, but not all, biochemical abnormalities in the diabetic heart.
Animals↗
Renal interstitial adenosine metabolism during ischemia in dogs.
The present study was conducted to determine the metabolism of renal interstitial adenosine under resting conditions and during ischemia. By using a microdialysis method with HPLC-fluorometric analysis, renal interstitial concentrations of adenosine, inosine, and hypoxanthine were assessed in pentobarbital-anesthetized dogs. Average basal renal interstitial concentrations of adenosine, inosine, and hypoxanthine were 0.18 +/- 0.04, 0.31 +/- 0.05, and 0.35 +/- 0.05 micromol/l, respectively. Local inhibition of adenosine kinase with iodotubercidin (10 micromol/l in perfusate) or inhibition of adenosine deaminase with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; 100 micromol/l in perfusate) did not change adenosine concentrations in the nonischemic kidneys (0.18 +/- 0.04 and 0.24 +/- 0.05 micromol/l, respectively). On the other hand, treatment with iodotubercidin+EHNA significantly increased adenosine concentration (0.52 +/- 0.07 micromol/l) with significant decreases in inosine and hypoxanthine levels (0.13 +/- 0.03 and 0.19 +/- 0.04 micromol/l, respectively). During 30 min of ischemia, adenosine, inosine, and hypoxanthine were significantly increased to 0.76 +/- 0.29, 2.14 +/- 0.45, and 21.8 +/- 4.7 micromol/l, respectively. The treatment with iodotubercidin did not alter ischemia-induced increase in adenosine (0.84 +/- 0.18 micromol/l); however, EHNA alone markedly enhanced adenosine accumulation (13.54 +/- 2.16 micromol/l), the value of which was not augmented by an addition of iodotubercidin (15.80 +/- 1.24 micromol/l). In contrast, ischemia-induced increases in inosine and hypoxanthine were inversely diminished by the treatment with iodotubercidin+EHNA (0.90 +/- 0.20 and 9.86 +/- 1.96 micromol/l, respectively). These results suggest that both adenosine kinase and adenosine deaminase contribute to the metabolism of renal interstitial adenosine under resting conditions, whereas adenosine produced during ischemia is mainly metabolized by adenosine deaminase and the rephosphorylation of adenosine by adenosine kinase is small.sent
Adenine↗
Interactions of adenosine A1 and A2a receptors on renal microvascular reactivity.
Adenosine vasoconstricts preglomerular arterioles via adenosine A1 receptors. Because adenosine also activates adenosine A2 receptors, its overall renal vascular actions are complex and not fully understood. The present study was performed to determine the relative contributions of adenosine A1 and A2a receptors to the responsiveness of the renal microvasculature to adenosine. Afferent and efferent arteriolar diameters were monitored in vitro using the blood-perfused rat juxtamedullary nephron preparation. Basal afferent and efferent arteriolar diameters averaged 17.1 +/- 0.5 (n = 35) and 17.8 +/- 0.5 (n = 20) microm, respectively. Superfusion with 0.1 and 1 micromol/l adenosine did not significantly alter afferent and efferent arteriolar diameters; however, 10 micromol/l adenosine significantly reduced afferent and efferent arteriolar diameters (-8.2 +/- 0.8 and -5.7 +/- 0.6%, respectively). The afferent and efferent arteriolar vasoconstrictor responses to adenosine waned at a dose of 100 micromol/l, such that diameters returned to values not significantly different from control within 2 min. During adenosine A1 receptor blockade with 8-noradamantan-3-yl-1,3-dipropylxanthine (KW-3902: 10 micromol/l), 10 and 100 micromol/l adenosine significantly increased afferent diameter by, respectively, 8.1 +/- 1.2 and 13.7 +/- 1.3% (n = 14) and efferent arteriolar diameter by 6.4 +/- 1.3 and 9.3 +/- 1.2% (n = 8). The afferent and efferent arteriolar vasodilatory responses to adenosine in the presence of KW-3902 were significantly attenuated by addition of the adenosine A2a receptor antagonist 1,3-dipropyl-7-methyl-8-(3,4-dimethoxystyryl)xanthine (KF-17837: 15 micromol/l, n = 7 and 6, respectively). The addition of KF-17837 alone significantly enhanced afferent (n = 15) and efferent (n = 6) arteriolar vasoconstrictor responses to 1, 10, and 100 micromol/l adenosine. These results indicate the presence of adenosine A1 and A2a receptors on afferent and efferent arterioles of juxtamedullary nephrons, such that adenosine A2a receptor-mediated vasodilation partially buffers adenosine-induced vasoconstriction in both pre- and postglomerular segments of the renal microvasculature.
Adenosine↗
Intrarenal formation of angiotensin II.
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Angiotensin II↗
Renal interstitial atp responses to changes in arterial pressure during alterations in tubuloglomerular feedback activity.
We recently demonstrated a direct relationship between autoregulation-related changes in renal vascular resistance (RVR) and renal interstitial ATP concentrations. To assess the possible role for extracellular ATP in the regulation of tubuloglomerular feedback (TGF)-mediated autoregulatory adjustments in RVR, renal interstitial ATP concentrations were measured with microdialysis probes in anesthetized dogs at different renal arterial pressures (RAPs) within the autoregulatory range during augmented and diminished activity of the TGF mechanism. Stepwise reductions in RAP from ambient pressure (129+/-3 mm Hg) to 102+/-2 mm Hg (step 1) and 75+/-1 mm Hg (step 2) resulted in significant decreases in ATP concentrations from 9.0+/-0.8 to 6.3+/-0.6 nmol/L in step 1 and to 4.2+/-0.5 nmol/L in step 2. Changes in RVR were highly correlated with changes in ATP concentrations (r=0.86, P<0.001, n=12). Acetazolamide (100 microgram. kg(-1). min(-1), n=6), which increases solute delivery to the macula densa, thus augmenting TGF activity, significantly decreased renal blood flow (RBF) by -16+/-2% and glomerular filtration rate (GFR) by -22+/-4% and increased ATP concentrations from 8.4+/-0.7 to 15.5+/-1.4 nmol/L. Although basal RBF and GFR levels were reduced by the acetazolamide infusion, autoregulation efficiency was maintained, and interstitial ATP concentrations were significantly decreased in response to reductions in RAP by -36+/-4% in step 1 and by -54+/-2% in step 2. The relationship between changes in RVR and interstitial ATP concentrations was preserved during acetazolamide treatment (r=0.80, P<0.01). Inhibition of the TGF mechanism by furosemide significantly increased RBF by 33+/-6% and GFR by 13+/-2% and decreased ATP concentrations from 8.9+/-1.4 to 5.0+/-0.8 nmol/L (n=6). Furosemide caused marked impairment of RBF and GFR autoregulatory efficiency (by -14+/-3% and -11+/-3% in step 1 and by -26+/-2% and -18+/-4% in step 2, respectively). In the furosemide-treated kidneys, interstitial ATP levels remained low and were not altered during reductions in RAP (4.7+/-0.7 nmol/L in step 1 and 4.7+/-0.8 nmol/L in step 2), and changes in RVR did not exhibit a correlation with changes in ATP concentrations (r=0.22, P=0.30). These data support the hypothesis that extracellular ATP contributes to autoregulatory adjustments in RVR that are mediated by changes in activity of the TGF mechanism.
Acetazolamide↗
Role of nitric oxide in regional blood flow in angiotensin II-induced hypertensive rats.
The present study was designed to evaluate the contribution of nitric oxide (NO) to regional hemodynamics during the early phase of angiotensin II (Ang II)-induced hypertension. The responses of regional blood flow to chronic NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) were assessed using radioactive microspheres in conscious Ang II-infused hypertensive rats. Ang II-infused rats (270 ng/kg/min, subcutaneously for 12 days: n=11) showed higher mean arterial pressure (MAP: 153+/-4 mmHg) and total peripheral resistance (TPR: 1.61+/-0.06 mmHg/min/ml), and lower cardiac output (CO: 102+/-3 ml/min) than vehicle-infused normotensive rats (115+/-2 mmHg, 0.96+/-0.05 mmHg/min/ml and 130+/-7 ml/min, n=11, respectively). The blood flow rates in the brain, spleen, large intestine and skin were significantly reduced in Ang III-infused rats compared with vehicle-infused rats, while those in the lung, heart, liver, kidney, adrenal gland, small intestine, and skeletal muscle were similar. Treating Ang II-infused rats with L-NAME (75 mg/l in drinking water for 10 days, n=11) resulted in higher MAP (166+/-6 mmHg) and TPR (1.89+/-0.18 mmHg/min/ml) and lower CO (87+/-7 m/min) than untreated Ang II-infused rats. L-NAME-treated Ang II-infused rats showed widespread increases in regional vascular resistance and reduced blood flow rates in the kidney (3.81+/-0.27 ml/min/g) and skeletal muscle (0.20+/-0.03 ml/min/g) compared with untreated Ang II-infused rats (6.88+/-0.27 and 0.33+/-0.04 ml/min/g, respectively). However, there were no significant differences in the flow rates of other organs investigated between these animals. An NO donor, (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409: 30 microg/kg/min, i.v.), significantly decreased MAP (110+/-6 mmHg) and TPR (1.23+/-0.18 mmHg/min/ml) without significant changes in CO (89+/-9 ml/min) in L-NAME-treated Ang II-infused rats. Furthermore, FK409 partially reversed blood flow rates in the kidney (4.72+/-0.40 ml/min/g) and skeletal muscle (0.25+/-0.02 ml/min/g)in these animals. These results suggest that NO counteracts, at least in part, the vasoconstrictor effects of elevated Ang II levels in renal and skeletal muscle vascular beds, and is an important modulator in the regulation of blood flow to these organs during the development of Ang II-induced hypertension.
Angiotensin II↗
Benidipine dilates both pre- and post-glomerular arteriole in the canine kidney.
The aim of the present study was to determine the effects of benidipine on renal function and whether benidipine may dilate the efferent arteriole as well as the afferent arteriole of the canine kidney. The effects of benidipine on the renal segmental vascular resistance were estimated using Gomez's formula with some modification. The renal hemodynamic action of benidipine was also compared with that of amlodipine. Intrarenal arterial injection of benidipine at a dose of 3 microg/kg resulted in a significant increase in renal blood flow (RBF), urine flow and urinary excretion of sodium, but not in glomerular filtration rate (GFR). Amlodipine at a dose of 300 microg/kg also increased RBF, urine flow and urinary excretion of sodium to a significant degree equivalent to that by benidipine. However, in contrast to benidipine, amlodipine significantly increased GFR. After the administration of benidipine, autoregulation of RBF and GFR was relatively maintained and the renal perfusion pressure (RPP)-RBF relation shifted upward; that is, RBFs at 75 and 50 mmHg were maintained at a higher level than those of the control. In contrast to benidipine, amlodipine diminished the autoregulation of RBF and GFR. RBFs at 75 and 50 mmHg were not different from those of the control. The afferent and efferent arteriolar resistance (Ra and Re) were calculated based on the RPP-RBF and RPP-GFR relations. Benidipine reduced both Ra and Re, but amlodipine selectively reduced Ra. Benidipine increased RBF but not GFR via the dilation of both afferent and efferent arterioles. Thus, benidipine has unique renal hemodynamic actions which differ from those by most calcium antagonists.
Animals↗
NG2 cells in the brain: a novel glial cell population.
There exists a significantly large population of glial cells in the mammalian central nervous system (CNS) that can be identified by the expression of the NG2 proteoglycan. Cells that express NG2 (NG2 cells) are found in the developing and mature CNS and are distinct from neurons, astrocytes, microglia, and mature oligodendrocytes. They are often referred to as oligodendrocyte progenitor cells because of their ability to differentiate into oligodendrocytes in culture. However, the observation that a large number of NG2 cells persist uniformly and ubiquitously in the adult CNS and display a differentiated morphology is not entirely consistent with the notion that NG2 cells are all oligodendrocyte progenitor cells. The role of NG2 cells in oligodendrocyte regeneration and their non-progenitor role in the mature CNS are discussed in this review.
Animals↗
A nonproteolytic function of the proteasome is required for the dissociation of Cdc2 and cyclin B at the end of M phase.
Inactivation of cyclin B-Cdc2 kinase at the exit from M phase depends on the specific proteolysis of the cyclin B subunit, whereas the Cdc2 subunit remains present at nearly constant levels throughout the cell cycle. It is unknown how Cdc2 escapes degradation when cyclin B is destroyed. In Xenopus egg extracts that reproduce the exit from M phase in vitro, we have found that dissociation of the cyclin B-Cdc2 complex occurred under conditions where cyclin B was tethered to the 26S proteasome but not yet degraded. The dephosphorylation of Thr 161 on Cdc2 was unlikely to be necessary for the dissociation of the two subunits. However, the dissociation was dependent on the presence of a functional destruction box in cyclin B. Cyclin B ubiquitination was also, by itself, not sufficient for separation of Cdc2 and cyclin B. The 26S proteasome, but not the 20S proteasome, was capable of dissociating the two subunits. These results indicate that the cyclin B and Cdc2 subunits are separated by the proteasome through a mechanism that precedes proteolysis of cyclin B and is independent of proteolysis. As a result, cyclin B levels decrease on exit from M phase but Cdc2 levels remain constant.
Animals↗