Biomedical subjects

Z Y Wang

Publications and source records attributed to Z Y Wang.

At least 19 recordsLinked to original sources

PubMed2006

Which has the least immunity depression during postoperative analgesia--morphine, tramadol, or tramadol with lornoxicam?

BACKGROUND: Analgesics are commonly used to provide pain relief after surgery. These drugs produce some extended depression of immunity. A prospective randomized controlled trial was designed to observe expressions of T-lymphocyte subsets (CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+)), natural-killer cells (CD3(-)CD16(+)CD56(+)), and activated T-lymphocytes (CD3(+)CD25(+)) of patients undergoing gastric cancer surgeries and receiving patient-controlled intravenous analgesia (PCIA). METHODS: Forty-five patients undergoing elective gastric cancer surgeries under general anesthesia were randomly allocated into 3 groups. Group I received PCIA using morphine after surgery, group II using tramadol, and group III using tramadol with lornoxicam. The analgesic efficacy was evaluated by visual analog scale (VAS) and Bruggrmann comfort scale (BCS). Expressions of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(-)CD16(+)CD56(+), and CD3(+)CD25(+) were measured as percentages of total lymphocytes by flow cytometer at 5 time points. RESULTS: There was no significant difference in analgesic efficacy and the baselines of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(-)CD16(+)CD56(+), and CD3(+)CD25(+) in all groups. Compared with the baseline, CD3(+)CD8(+) had no changes in all groups at any time point. Ninety minutes after incision, CD3(+), CD3(+)CD4(+), CD3(-)CD16(+)CD56(+), and CD3(+)CD25(+) were lower in all groups (P<0.05). 24 h after surgery, CD3(+), CD3(+)CD4(+), CD3(-)CD16(+)CD56(+), and CD3(+)CD25(+) were lower in group I and group II (P<0.05); meanwhile CD3(+), CD3(+)CD4(+), and CD3(+)CD25(+) returned to the baseline but CD3(-)CD16(+)CD56(+) was still low (P<0.05) in group III. 48 h after surgery, CD3(+), CD3(+)CD4(+), CD3(-)CD16(+)CD56(+), and CD3(+)CD25(+) returned to the baseline in group II and group III, but not in group I (P<0.05). 72 h after surgery, CD3(+), CD3(+)CD4(+), CD3(+)CD4(+)/CD3(+)CD8(+) returned to the baseline, but CD3(+)CD25(+) and CD3(-)CD16(+)CD56(+) were still low in group I (P<0.05). CONCLUSION: PCIA using lornoxicam with tramadol has the same good analgesic efficacy and less immunity depression than PCIA using morphine or tramadol.

Adult↗

PubMed2006

Expression and preliminary characterization of recombinant human tissue kallikrein in egg white of laying hens.

Human tissue kallikrein (hK1) plays an important role in regulation of blood pressure, electrolyte and glucose transport, and renal function. To evaluate the feasibility of expression of recombinant human tissue kallikrein (rhK1) in the egg whites of laying hens, human tissue kallikrein gene (hKLK1) cDNA was subcloned into the chicken oviduct-specific expression vector (pOV3), and the resultant recombinant vector pOV3K was injected into laying hens via wing vein after mixing with polyethyleneimine. Following injection twice with the recombinant vector, the enzymatic activity at a maximal level of 59 U/mL was detected in the egg whites, which lasted for more than 7 d. The expression level of rhK1 in the egg whites in the 3-mg group was relatively higher than that in the 2-mg group, but the significant differences were identified on d 7 and 8 (P < 0.05). Ten days after the primary injection, the hens were reinjected with the same dose of the vector, and even higher enzymatic activity was detected in their egg whites. Two different breeds of hen were tested with no difference in expression level found (P > 0.05). Western blot analysis of the egg whites from vector-injected hens showed the rhK1 was recognized by a polyclonal antibody specific for hK1 with molecular weights of 37 and 43 kDa, which probably corresponded to the mature and preenzyme, respectively. Biochemical studies showed that the recombinant enzyme had a similar thermostability, optimal pH, hypotensive effect, and sensitivity to different ions to the natural enzymes in human and porcine tissues. These data indicate that the chicken oviduct-specific transient expression system can produce relatively high level and authentic recombinant enzyme with a potential for further development for therapeutic use.

Animals↗

PubMed2006

[Codon usage of Chinese hamster ovary cells.].

BACKGROUND: To investigate the optimal codons of dihydrofolate reductase (dhfr) minus Chinese hamster ovary cells (CHO dhfr-). METHODS: A cDNA library of CHO dhfr- containing high abundence mRNA was constructed and protein-coding sequences were obtained after identification and analysis. Codon frequence of CHO dhf- was compared with that of Chinese hamster in CUTG database. Then codon usage variation among cDNA was investigated using correspondence analysis (COA). RESULTS: Fifty qualified cDNAs from CHO dhfr- were selected, which encodes proteins of high abundence. Comparing with the codon frequence of Chinese hamster, the highest frequence of synonymous codons for amino acids in CHO dhfr- cells were the same as Chinese hamster except that of Arg and Pro. This method of COA identifies the first main factor which can account for the largest fractions (14.7%) of variation among cDNAs. Twenty-two synonymous codons were identified as the optimal codons of CHO cell. CONCLUSION: CHO dhfr- cell has its own optimal codons, it is suggested that codon bias is one of reasons for functional diversity of different mammal cells and it is an effective stratagy to modification of the codon usage of the foreign gene according to the optimal codons of CHO dhfr- to increase the production of foreign gene.

Animals↗

PubMed2005

Marked hypotension induced by adrenaline contained in local anesthetic.

OBJECTIVES: Local anesthetics containing adrenaline, which often cause cardiovascular side effects, are routinely used in functional endoscopic sinus surgery (FESS) for the main purpose of hemostasis. The controversies concerning hemodynamic effects of adrenaline in local infiltration are widely discussed, but there is no definite conclusion. A prospective, randomized, double-blinded study was carried out to discover the hemodynamic effects after local infiltration of 1:200,000 adrenaline contained in 2% lidocaine under general anesthesia. STUDY DESIGN: Seventy-six adult patients undergoing FESS during general anesthesia were allocated randomly into three groups. Group I patients (n = 26) received 2% lidocaine 2 mL with adrenaline (1:200,000), group II patients (n = 25) received saline 2 mL with adrenaline (1:200,000), and group III patients (control group, n = 25) received saline 2 mL without adrenaline for local infiltration. Electrocardiogram (ECG) and heart rate (HR) were monitored simultaneously; systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MAP) were directly measured in radial artery continuously after local infiltration. METHODS: SBP, DBP, MAP, and HR were recorded at 10 time points: before infiltration (baseline), 0.5 minutes, 1 minute, 1.5 minutes, 2 minutes, 2.5 minutes, 3 minutes, 3.5 minutes, 4 minute, and 5 minutes after infiltration. RESULTS: Significant hemodynamic changes, particularly hypotension (P < .01), after local infiltration were observed in group I and group II compared with the baseline, but not in group III. However, there were no significant hemodynamic changes between group I and group II at the same time points (P > .05). The significant hemodynamic changes lasted no longer than 4 minutes. CONCLUSIONS: Lidocaine (2%) or saline with adrenaline (1:200,000) does cause temporary hypotension and other hemodynamic changes during general anesthesia, which last no longer than 4 minutes. The causative mechanism is caused by the effect of adrenaline. This is a preliminary study.

Anesthesia, General↗

PubMed2005

Local anesthesia for functional endoscopic sinus surgery employing small volumes of epinephrine-containing solutions of lidocaine produces profound hypotension.

BACKGROUND: Local anesthetic containing epinephrine is commonly used in many operations for the main purpose of hemostasis. A randomized, controlled, prospective clinical trial was designed to find out hemodynamic changes after local infiltration of different concentrations and/or different dosages of epinephrine during functional endoscopic sinus surgery (FESS) under general anesthesia. METHODS: One hundred and eight adult patients undergoing elective FESS under general anesthesia were randomly allocated into four groups. Group I received 2% lidocaine 2 ml with epinephrine (5 microg/ml); group II received 1% lidocaine 4 ml with epinephrine (2.5 microg/ml); group III received 1% lidocaine 4 ml with epinephrine (5 microg/ml); and group IV received 1% lidocaine 4 ml for local infiltration. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were monitored continuously in the radial artery and recorded in 6 min: before infiltration (baseline), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 min after local infiltration. The lowest blood pressure (BP) in this period was also recorded. RESULTS: Significant hemodynamic changes, particularly a decrease in BP (P < 0.001) with a slight increase in HR (P < 0.001) at approximately 1.5 min and an increase in SBP at approximately 3 min (P < 0.01) after local infiltration, were observed in group I, group II and group III compared with the baseline, but not in group IV. No significant hemodynamic differences were observed between group I, group II and group III at the same time points (P > 0.05). CONCLUSION: Local infiltration of low-dose epinephrine causes temporary significant hemodynamic changes particularly a marked decrease in BP during FESS under general anesthesia.

Adolescent↗

PubMed2005

Single-crystal CdSe nanowires prepared via vapor-phase growth assisted with silicon.

Hexagonal cadmium selenide (CdSe) nanowires, with diameter around 20 nm, were synthesized using a simple vapor-phase growth. Silicon (Si) powder acts as a source material assisting the synthesis, which is very important to the formation of the CdSe nanowires. We also suggest that self-catalysis at the Cd-terminated (0001) surface, together with the assistance action of Si, leads to the formation of wire-like structures to be formed. Meanwhile, the assistance of Si is responsible for the fineness and uniformity of the CdSe nanowires. The possible growth mechanism of the CdSe nanowires is proposed, and the optical property of the as-grown CdSe nanowires is characterized.

Cadmium Compounds↗

PubMed2005

Adjusting lung cancer risks for temporal and spatial variations in radon concentration in dwellings in Gansu Province, China.

Our recent study in Gansu Province, China reported an increasing risk of lung cancer with increasing residential radon concentration that was consistent with previous pooled analyses and with meta-analyses of other residential studies (Wang et al., Am. J. Epidemiol. 155, 554-564, 2002). Dosimetry used current radon measurements (1-year track-etch detectors) in homes to characterize concentrations for the previous 30 years, resulting in uncertainties in exposure and possibly reduced estimates of disease risk. We conducted a 3-year substudy in 55 houses to model the temporal and spatial variability in radon levels and to adjust estimates of radon risk. Temporal variation represented the single largest source of uncertainty, suggesting the usefulness of multi-year measurements to assess this variation; however, substantial residual variation remained unexplained. The uncertainty adjustment increased estimates of the excess odds ratio by 50-100%, suggesting that residential radon studies using similar dosimetry may also underestimate radon effects. These results have important implications for risk assessment.

Adult↗

PubMed2003

Field performance of transgenic tall fescue (Festuca arundinacea Schreb.) plants and their progenies.

Tall fescue (Festuca arundinacea Schreb.) is a hexaploid, outcrossing grass species widely used for forage and turf purposes. Transgenic tall fescue plants were generated by biolistic transformation of embryogenic cell suspension cultures that were derived from single genotypes of widely used cultivar Kentucky-31. Primary transgenics from two genotypes, their corresponding regenerants from the same genotypes and control seed-derived plants were transferred to the field and evaluated for 2 years. Progenies of these three classes of plants were obtained and evaluated together with seed-derived plants in a second field experiment. The agronomic characteristics evaluated were: heading date, anthesis date, height, growth habit, number of reproductive tillers, seed yield and biomass. The agronomic performance of the primary transgenics and regenerants was generally inferior to that of the seed-derived plants, with primary transgenics having fewer tillers and a lower seed yield. However, no major differences between the progenies of transgenics and the progenies of seed-derived plants were found for the agronomic traits evaluated. Primary transgenics and regenerants from the same genotype were more uniform than plants from seeds. Progenies of transgenics performed similarly to progenies of the regenerants. The addition of a selectable marker gene in the plant genome seems to have had little effect on the agronomic performance of the regenerated plants. No indication of weediness of the transgenic tall fescue plants was observed. Our results indicate that outcrossing grass plants generated through transgenic approaches can be incorporated into forage breeding programs.

Biolistics↗

PubMed2003

Zinc transporter 3 and zinc ions in the rodent superior cervical ganglion neurons.

Previous studies have revealed that zinc-enriched (ZEN) terminals are present in all parts of the CNS though with great differences in intensity. The densest populations of both ZEN terminals and ZEN somata are found in telencephalic structures, but also structures like the spinal cord demonstrate impressive ZEN systems spreading terminals several segments around the respective ZEN somata. The present study evaluates whether sympathetic neurons in the superior cervical ganglia (SCG) are ZEN neurons, i.e. contain vesicles that have zinc transporter 3 (ZnT3) proteins in their membranes and contain zinc ions. ZnT3 immunoreactivity (IR) was found in the somata and processes in the postganglionic neurons of mouse SCG. Only a small fraction of neurons (less than 5%), expressed varying degrees of ZnT3. Colchicine treatment, however, increased the number of ZnT3-positive neurons three-fold, suggesting an accumulation of ZnT3 protein in the somata. A small proportion of the postganglionic axons revealed dotted accumulations of ZnT3 IR along their courses. Double labeling showed that all ZnT3-positive neurons and axons were also tyrosine hydroxylase-positive with strong immunofluorescence, while no colocalization was found between ZnT3 and the vesicular acetylcholine transporter (VAChT) or neuropeptide Y IR. VAChT-positive preganglionic neurons were found to terminate on ZnT3 neuronal somata. 6-Methoxy 8-para toluene sulfonamide quinoline fluorescence and zinc selenium autometallography (ZnSe(AMG)) revealed that a subgroup of SCG cells contained free or loosely bound zinc ions. It is therefore concluded that ZnT3 and zinc ions are present in a subpopulation of TH-positive, NPY-negative neurons in the rodent SCG, supporting the notion that vesicular zinc ions may play a special role in the peripheral sympathetic adrenergic system.

Animals↗

PubMed2003

Progesterone induces the proliferation of urothelial cells in an epidermal growth factor dependent manner.

PURPOSE: We have previously reported that estrogen induced proliferation of urothelial cells is modulated by nerve growth factor (NGF). In this study we investigated whether progesterone induces urothelial cell proliferation and whether this effect is modulated by NGF or by epidermal growth factor (EGF). MATERIALS AND METHODS: Experiments were performed using human urothelial cells immortalized by human papillomavirus E6. Cell proliferation was determined using the alamarBlue (Trek Diagnostic, Westlake, New York) assay. Human papillomavirus were seeded in 48-well plates. They were incubated with 5% alamarBlue and different concentrations of progesterone, EGF or NGF in the presence or absence of neutralizing EGF or NGF antibody, K252a (an inhibitor of trkA, the high affinity receptor for NGF), Ru-486 (an antagonist of progesterone and glucocorticoid receptor) or ZK 137 316 (a specific antagonist of progesterone receptor). Immunoblotting was performed using specific antibodies for progesterone receptor, glucocorticoid receptor or EGF receptor. EGF content in conditioned medium was determined by enzyme-linked immunosorbent assay. RESULTS: In the presence of 10 nM to 1 microM progesterone urothelial cell proliferation was significantly increased 8.6% to 51.1%. This effect was abolished by ZK137 316 or by Ru-486. Hydrocortisone also induced urothelial cell proliferation. This effect was blocked by Ru-486 but not by ZK137 316. In addition, progesterone stimulated urothelial cell proliferation was inhibited by neutralizing EGF antibody but not by NGF antiserum or K252a. We also found that EGF synthesis and release by urothelial cells was increased by exogenous progesterone. This effect of progesterone was inhibited by ZK 137 316. CONCLUSIONS: These findings indicate that progesterone has the capacity to induce urothelial cell proliferation through its cognate receptor and this effect is mediated by EGF but not by NGF.

Carbazoles↗

PubMed2001

Induced recovery of hypoxic phrenic responses in adult rats exposed to hyperoxia for the first month of life.

1. Adult rats exposed to hyperoxia for the first month of life have permanently attenuated ventilatory and phrenic nerve responses to hypoxia. We tested the hypothesis that the blunted hypoxic phrenic response in hyperoxia-treated rats (inspired O(2) fraction, F(I,O2) = 0.6 for 28 post-natal days) could be actively restored to normal by intermittent (alternating 12 % O(2)/air at 5 min intervals; 12 h per night for 1 week) or sustained (12 % O(2) for 1 week) hypoxia. 2. Phrenic responses to isocapnic hypoxia (P(a,O2) = 60, 50 and 40 +/- 2 mmHg) were assessed in the following groups of anaesthetized, vagotomized adult Sprague-Dawley rats (age 4 months), treated with a neuromuscular blocking agent and ventilated: control, hyperoxia-treated and hyperoxia-treated exposed to either intermittent or sustained hypoxia as adults. Experiments on intermittent and sustained hypoxia-treated rats were performed on the morning following hypoxic exposures. 3. Both intermittent and sustained hypoxia enhanced hypoxic phrenic responses in hyperoxia-treated rats when expressed as minute phrenic activity (P < 0.05). Increases in phrenic burst amplitude during hypoxia were greater in hyperoxia-treated rats after intermittent hypoxia (P < 0.05), and a similar but non-significant trend was observed after sustained hypoxia. Hypoxia-induced changes in phrenic burst frequency were not significantly different among groups. 4. The estimated carotid body volume in control rats (11.5 (+/- 0.7) x 10(6) microm(3)) was greater than in the other treatment groups (P < 0.05). However, carotid body volume was significantly greater in hyperoxia-treated rats exposed to sustained hypoxia (6.3 (+/- 0.3) x 10(6) microm(3); P < 0.05) compared to hyperoxia-treated rats (3.3 (+/- 0.2) x 10(6) microm(3)) or hyperoxia-treated rats exposed to intermittent hypoxia (3.8 (+/- 0.3) x 10(6) microm(3)). 5. Hypoxic phrenic responses in hyperoxia-treated rats 1 week after intermittent hypoxia were similar to responses measured immediately after intermittent hypoxia, indicating persistent functional recovery. 6. The results indicate that diminished hypoxic phrenic responses in adult rats due to hyperoxia exposure for the first 28 post-natal days can be reversed by intermittent or sustained activation of the hypoxic ventilatory control system. Although the detailed mechanisms of functional recovery are unknown, we suggest that sustained hypoxia restores carotid chemoreceptor sensitivity, whereas intermittent hypoxia primarily augments central integration of synaptic inputs from chemoafferent neurons.

Animals↗

PubMed2001

Arsenic trioxide, a therapeutic agent for APL.

Acute promyelocytic leukemia (APL) is an interesting model in cancer research, because it can respond to the differentiation/apoptosis induction therapy using all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)). Over the past 5 years, it has been well demonstrated that As(2)O(3) induces a high complete remission (CR) rate in both primary and relapsed APL patients (around 85 to 90%). The side effects are mild to moderate in relapsed patients, while severe hepatic lesions have been found in some primary cases. After CR obtained in relapsed patients, chemotherapy in combination with As(2)O(3) as post-remission therapy has given better survival than those treated with As(2)O(3) alone. The effect of As(2)O(3) has been shown to be related to the expression of APL-specific PML-RARalpha oncoprotein, and there is a synergistic effect between As(2)O(3) and ATRA in an APL mouse model. Cell biology studies have revealed that As(2)O(3) exerts dose-dependent dual effects on APL cells. Apoptosis is evident when cells are treated with 0.5 approximately 2.0 microM of As(2)O(3) while partial differentiation is observed using low concentrations (0.1 approximately 0.5 microM) of the drug. The apoptosis-inducing effect is associated with the collapse of mitochondrial transmembrane potentials in a thiol-dependent manner, whereas the mechanisms underlying APL cell differentiation induced by low dose arsenic remain to be explored. Interestingly, As(2)O(3) over a wide range of concentration (0.1 approximately 2.0 microM) induces degradation of a key leukemogenic protein, PML-RARalpha, as well as the wild-type PML, thus setting up a good example of targeting therapy for human cancers.

Animals↗

PubMed2001

All trans retinoic acid in acute promyelocytic leukemia.

All trans retinoic acid (ATRA) is able to induce complete remission (CR) in almost all patients with acute promyelocytic leukemia (APL) through in vivo differentiation of APL blasts. However, it cannot eliminate the leukemic clone and to be effective must be used in combination with anthracycline-based chemotherapy. Experience accumulated over the last 10 years has clearly shown that the combination of ATRA and chemotherapy gives better survival in newly diagnosed APL than chemotherapy alone because of fewer relapses and a higher CR rate experienced by these patients. It is also strongly suggested that maintenance treatment with ATRA, and possibly in combination with low-dose chemotherapy, can further reduce the incidence of relapse. Overall, more than 90% of patients with newly diagnosed APL can achieve CR and about 75% can be cured by the combination of ATRA and chemotherapy.

Age Factors↗

PubMed2001

Rb-associated protein 46 (RbAp46) suppresses the tumorigenicity of adenovirus-transformed human embryonic kidney 293 cells.

The retinoblastoma suppressor (Rb)-associated protein 46 (RbAp46) is a nuclear protein of the WD-repeat protein family and a component of the histone deacetylase complex that physically interacts with Rb. We demonstrated that RbAp46 is a gene up-regulated by the Wilms' tumor suppressor (WT1) and functions as a negative regulator of cell growth. Here we have investigated the ability of RbAp46 to inhibit malignant phenotype of adenovirus-transformed human embryonic kidney (HEK) 293 cells in tumorigenesis assays. We have found that expression of RbAp46 suppressed clonal growth of HEK 293 cells in soft agar and inhibited tumor growth of these cells in nude mice. Furthermore, expression of RbAp46 resulted in an increase of cells in the G2/M fraction of cell cycle and augmented apoptosis in serum-starved cells. The results suggest that high levels of RbAp46 expression inhibit the transformation of tumor cells through interfering with normal cell cycle and/or enhancing apoptotic cell death.

Adenoviridae↗

PubMed2001

Is the postganglionic sympathetic neuron zinc-enriched? A stop-flow nerve crush study on rat sciatic nerve.

Axonal transport of endogenous zinc ions in the rat sciatic nerve was studied by a stop-flow/nerve crush technique combined with zinc selenide autometallography (ZnSeAMG) at light and electron microscopic levels. Distinct accumulations of ZnSeAMG grains were detected, in particular proximal but also distal to the crushes, 1.5 h after the operation, and the amounts of zinc ions increased further in the following 3-8 h. Ultrastructurally, ZnSeAMG grains were located predominantly in unmyelinated axons. The data suggest that a subpopulation of sciatic nerve axons contains and transports zinc ions both antero- and retrogradely, indicating that the second neuron in the sympathetic nervous system is zinc enriched (ZEN).

Animals↗

PubMed2001

Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice.

Heme oxygenase (HO)-1 degrades the pro-oxidant heme and generates carbon monoxide and antioxidant bilirubin. We have previously shown that in response to hypoxia, HO-1-null mice develop infarcts in the right ventricle of their hearts and that their cardiomyocytes are damaged by oxidative stress. To test whether HO-1 protects against oxidative injury in the heart, we generated cardiac-specific transgenic mice overexpressing different levels of HO-1. By use of a Langendorff preparation, hearts from transgenic mice showed improved recovery of contractile performance during reperfusion after ischemia in an HO-1 dose-dependent manner. In vivo, myocardial ischemia and reperfusion experiments showed that infarct size was only 14.7% of the area at risk in transgenic mice compared with 56.5% in wild-type mice. Hearts from these transgenic animals had reduced inflammatory cell infiltration and oxidative damage. Our data demonstrate that overexpression of HO-1 in the cardiomyocyte protects against ischemia and reperfusion injury, thus improving the recovery of cardiac function.

Animals↗

PubMed2001

Rb-associated protein 46 (RbAp46) inhibits transcriptional transactivation mediated by BRCA1.

The retinoblastoma suppressor (Rb)-associated protein 46 (RbAp46) is a member of the WD-repeat protein family and a component of the histone modifying and remodeling complexes. Previously, we demonstrated that RbAp46 is a potent growth inhibitor that can suppress the transformed phenotype of tumor cells. To explore the molecular mechanisms of RbAp46 function, we used RbAp46 as a bait in a yeast two-hybrid screening and found that RbAp46 interacts specifically with the C-terminal region of BRCA1 (the BRCT domain), a domain involved in the t transactivation activity of BRCA1. Coimmunoprecipitation assays demonstrated that the interaction of RbAp46 with BRCA1 requires the first two of the four Trp-Asp (WD)-repeats of RbAp46. We also showed that expression of RbAp46 represses the transactivation activity mediated by the BRCT/Gal4 fusion protein and inhibits the transactivation of the p21 promoter mediated by the full-length BRCA1. Interestingly, the association of BRCA1 and RbAp46 is disrupted in cells treated with DNA-damaging agents. These results suggest that RbAp46 may specifically interact with BRCA1 and modulate its transactivation activity in response to DNA damage.

BRCA1 Protein↗

PubMed2001

Exacerbation of chronic renovascular hypertension and acute renal failure in heme oxygenase-1-deficient mice.

Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Because of properties of HO and its products, we hypothesized that HO would be important for the regulation of blood pressure and ischemic injury. We studied chronic renovascular hypertension in mice deficient in the inducible isoform of HO (HO-1) using a one kidney-one clip (1K1C) model of disease. Systolic blood pressure was not different between wild-type (HO-1(+/+)), heterozygous (HO-1(+/-)), and homozygous null (HO-1(-/-)) mice at baseline. After 1K1C surgery, HO-1(+/+) mice developed hypertension (140+/-2 mm Hg) and cardiac hypertrophy (cardiac weight index of 5.0+/-0.2 mg/g) compared with sham-operated HO-1(+/+) mice (108+/-5 mm Hg and 4.1+/-0.1 mg/g, respectively). However, 1K1C produced more severe hypertension (164+/-2 mm Hg) and cardiac hypertrophy (6.9+/-0.6 mg/g) in HO-1(-/-) mice. HO-1(-/-) mice also experienced a high rate of death (56%) within 72 hours after 1K1C surgery compared with HO-1(+/+) (25%) and HO-1(+/-) (28%) mice. Assessment of renal function showed a significantly higher plasma creatinine in HO-1(-/-) mice compared with HO-1(+/-) mice. Histological analysis of kidneys from 1K1C HO-1(-/-) mice revealed extensive ischemic injury at the corticomedullary junction, whereas kidneys from sham HO-1(-/-) and 1K1C HO-1(+/-) mice appeared normal. Taken together, these data suggest that chronic deficiency of HO-1 does not alter basal blood pressure; however, in the 1K1C model an absence of HO-1 leads to more severe renovascular hypertension and cardiac hypertrophy. Moreover, renal artery clipping leads to an acute increase in ischemic damage and death in the absence of HO-1.

Acute Kidney Injury↗