Potential role of aquaporins and atrial natriuretic peptides in the aqueous humor dynamics.
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Animals↗
Biomedical subjects
Z Han
Publications and source records attributed to Z Han.
Neoplastic transformation of hamster embyro cells by heavy ions.
We have studied the induction of morphological transformation of Syrian hamster embryo cells by low doses of heavy ions with different linear energy transfer (LET), ranging from 13 to 400 keV/micrometer. Exponentially growing cells were irradiated with 12C or 28Si ion beams generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC), inoculated to culture dishes, and transformed colonies were identified when the cells were densely stacked and showed a crisscross pattern. Over the LET range examined, the frequency of transformation induced by the heavy ions increased sharply at very low doses no greater than 5 cGy. The relative biological effectiveness (RBE) of the heavy ions relative to 250 kVp X-rays showed an initial increase with LET, reaching a maximum value of about 7 at 100 keV/micrometer, and then decreased with the further increase in LET. Thus, we confirmed that high LET heavy ions are significantly more effective than X-rays for the induction of in vitro cell transformation.
Animals↗
A cytosolic factor is required for mitochondrial cytochrome c efflux during apoptosis.
Treatment of HL-60 cells with staurosporine (STS) induced mitochondrial cytochrome c efflux into the cytosol, which was followed by caspase-3 activation and apoptosis. Consistent with these observations, in vitro experiments demonstrated that, except for cytochrome c, the cytosol of HL-60 cells contained sufficient amounts of all factors required for caspase-3 activation. In contrast, treatment of HCW-2 cells (an apoptotic-resistant HL-60 subclone) with STS failed to induce significant amounts of mitochondrial cytochrome c efflux, caspase-3 activation, and apoptosis. In vitro assays strongly suggested that a lack of cytochrome c in the cytosol was the primary limiting factor for caspase-3 activation in HCW-2 cells. To explore the mechanism which regulates mitochondrial cytochrome c efflux, we developed an in vitro assay which showed that cytosolic extracts from STS-treated, but not untreated, HL-60 cells contained an activity, which we designated 'CIF' (cytochrome c-efflux inducing factor), which rapidly induced cytochrome c efflux from HL-60 mitochondria. In contrast, there was no detectable CIF activity in STS-treated HCW-2 cells although the mitochondria from HCW-2 cells were responsive to the CIF activity from STS-treated HL-60 cells. These experiments have identified a novel activity, CIF, which is required for cytochrome c efflux and they indicate that the absence of CIF is the biochemical explanation for the impaired ability of HCW-2 cells to activate caspase-3 and undergo apoptosis.
Apoptosis↗
The homeobox-containing gene Wariai regulates anterior-posterior patterning and cell-type homeostasis in Dictyostelium.
We have identified a Dictyostelium gene, Wariai (Wri), that encodes a protein with a homeobox and seven ankyrin repeats; both domains are required for function. A null mutation results in a more than doubling of the size of the prestalk O (pstO) compartment, one of the anterior prestalk compartments lying along the anterior-posterior axis of the migrating slug. There is a concomitant decrease in the more posterior prespore domain and no change in the more anterior prestalk A (pstA) and prestalk AB (pstAB) domains. wri null cells also have a morphological defect consistent with an increase in the pstO cell population. Wri itself is preferentially expressed in the pstA but not the pstO compartment, raising the possibility that Wri regulation of pstO compartment size is nonautonomous. Analysis of chimeric organisms is consistent with this model. Development in Dictyostelium is highly regulative, with cells within the prestalk and prespore populations being able to transdifferentiate into other cells to maintain proper cell-type proportioning. Our results suggest that Wri controls cell-type proportioning, possibly by functioning as a negative regulator of a pathway mediating pstO cell differentiation and controlling the mechanism of homeostasis regulating the size of one or more of the cell-type compartments. Our results also suggest that homeobox gene regulation of anterior-posterior axis patterning may have evolved prior to the evolution of metazoans.
Amino Acid Sequence↗
AP-1 and NF-kappaB regulation in rheumatoid arthritis and murine collagen-induced arthritis.
OBJECTIVE: To determine the expression and regulation of nuclear transcription factors AP-1 and NF-kappaB in rheumatoid arthritis and in collagen-induced arthritis in mice. METHODS: AP-1 and NF-kappaB expression and function were determined in RA, OA and normal synovial tissue by electrophoretic mobility shift assay (EMSA) and immunohistochemistry. The kinetics of transcription factor expression were then examined in collagen-induced arthritis (CIA) in mice. EMSAs were performed with the nuclear extracts obtained from paws of CIA mice from 10 to 45d after immunization to determine AP-1 and NF-kappaB binding activity. The expression of collagenase-3 (MMP13) and stromelysin (MMP3) mRNA was examined by northern blot analysis. RESULTS: Immunohistochemistry showed that NF-kappaB expression was increased in both RA and OA synovial intimal lining. AP-1 components Jun and Fos were also present in the intimal lining and was significantly greater in RA than OA. The DNA binding activities of both AP-1 and NF-kappaB were significantly higher RA patients compared with OA. In CIA, AP-1 and NF-kappaB expression increased by day 20, which was 1-2 weeks before onset of clinical arthritis. However, collagenase and stromelysin gene expression did not increase until day 35. CONCLUSION: The DNA binding activity of AP-1 and NF-kappaB are markedly increased in both CIA and RA. In CIA, activation of AP-1 and NF-kappaB precede both clinical arthritis and metalloproteinase gene expression. NF-kappaB expression correlated better than AP-1 with metalloproteinase expression.
Animals↗
Effects of electroacupuncture at neiguan on myocardial microcirculation in rabbits with acute myocardial ischemia.
This paper reports the effects of electroacupuncture (EA) at Neiguan (P 6) on myocardial microcirculation and electrical activity observed in rabbits with acute myocardial ischemia (AMI) by employing the vascular casting method and taking monophasic action potential (MAP) as an index. It was found that in the ischemic border zone of the heart, the electrical excitability was strengthened, the shortening of the phase repolarization inhibited, and the number of the micrangia increased in some degree following EA. This suggests that EA can relieve arteriolospasm, inhibit extreme dilatation of blood capillaries, modulate imbalance of micro-vasomotion of the coronary artery, improve myocardial blood-supply, and promote normalization of electrical activities of the ischemia myocardium. This fact not only elucidates the recovery mechanism of the ischemic myocardium promoted by EA at Neiguan (P 6), but also provides morphological basis for the theory of relationship between Neiguan of the Pericardium Meridian and the heart.
Action Potentials↗
[Effects of mifepristone on proliferation and apoptosis in early chorionic villi].
OBJECTIVE: To study the effects of mifepristone on proliferation and apoptosis in early pregnant chorionic villi. METHODS: Proliferation and apoptosis in early pregnant choionic villi from surgical aspiration and mifepristone induced abortion were studied. Marker for proliferation is proliferating cell nuclear antigen (PCNA) immunohistochemical staining, apoptotic cell death was detected using DNA in situ terminal deoxynucleotidyl transferas-mediated dUTP-biotin nick ending labeling (TUNEL). RESULTS: In early pregnant chorionic villi, proliferating index of cytotrophoblasts was 53.74% +/- 1.34%, not only nuclear but also cytoplasma were PCNA positive staining, syncytiotrophoblasts were negative. There existed apoptotic cell death in trophoblasts, the apoptotic index were 2.52% +/- 0.86% in syncytiotrophoblasts and 0.52% +/- 0.26% in cytotrophblasts, respectively. After 2 days mifepristone treatment, the proliferating index of cytotrophoblasts decreased slightly and PCNA positive cytoplasmic expression disappeared; while apoptotic cell increased significantly, the apoptotic indices were 22.16% +/- 2.26% in syncytiotrophoblasts and 20.12% +/- 1.74% in cytotrophoblasts, respectively. CONCLUSION: Mifepristone may inhibit proliferation and promote apoptosis of trophoblasts in early pregnant chorionic villi.
Abortifacient Agents, Steroidal↗
[Semiquantitative measurement of progesterone receptors in luteal-phase-defect endometrial cells during secretory phase].
To investigate the changes of endometrial progesterone receptor (PR) of luteal-phase-defect (LPD) patients during the secretory phase, thirteen patients with complaints of infertility or habitual abortion were studied. During the early-mid secretory phase, endometrial tissue was obtained by dilatation and curettage (D & C) for histological and receptor study: meanwhile serum E2, P, FSH, LH and PRL were measured. Based on histologic diagnosis, the patients were divided into two groups: the LPD group (n = 7) and the normal control group(n = 6). PR content was determined by immunohisto-chemical (IHC) assay. The results showed that during the early-mid luteal phase a significantly low PR content on endometrial glandular nucleus was observed in LPD group, compared with normal control(6.75 +/- 2.57 vs 9.50 +/- 1.64 P < 0.05), but no difference in serum progesterone was noted between the two groups. These findings suggest that during early-mid secretory phase, PR content on endometrial glandular nucleus decreases in LPD cases, which results in deficient response of endometrium to proper stimulus of progesterone. This change may cause endometrial secretory deficiency and blockade of embreyo implantation. That is why infertility or habitual abortion happened.
Abortion, Habitual↗
[Effects of mifepristone on ICE expression and Fas expression in early pregnant chorionic villi].
This study addressed the question whether mifepristone has any effect on apoptosis in early pregnant chorionic villi. Interleukin 1 beta converting enzyme(ICE) expression and Fas expression in early pregnant villi and their changes following mifepristone administration were detected by immunohistochmical method and computer image analysis. During early pregnancy, ICE and Fas were expressed in all component chorionic cells, predominantly syncytiotrophoblasts. ICE stained cytoplasma. Fas stained mainly cytoplasma, and in partial trophoblastic cells, Fas was expressed on membrane and nucleus. In the villi from the pregnant women who received mifepristone for 2 days, expression of Fas increased markely; the ratio of positive nuclear staining cells were significantly raised, but the immunostaining intensity of ICE was slightly increased. These results suggest that mifepristone may terminate early pregnancy via increasing the expression of Fas and promoting apoptosis in the chorionic villi.
Abortifacient Agents, Steroidal↗
[Reconstruction with silicone rubber tube after resection of hypopharyngeal and cervical esophageal cancer].
OBJECTIVE: To treat the benign stenosis and defects caused by resection of cancers of hypopharyngeal and cervical esophagus. METHODS: Silicone rubber tubes made by ourselves were utilized to reconstruct the defect. It was found that in animal models, the granulation surface was covered with epithelial tissues and new lumen formed. RESULTS: Among 30 cases treated with silicone rubber tubes, 6 cases (20.0%) developed hypopharyngeal fistulae after operations. Twenty-five cases with cancer and 5 cases with benign stenoses and hypopharyngeal fistulae were followed-up from 5 months to 4 years. The silicone rubber tubes in 25 cases were decannulated, of them, 23 cases recovered normal swallowing function. Two cases developed severe stenosis again and 2 cases were under observation. In 25 cases with cancer, 2 had local relapse of cancer three to six months after the first operation. Four cases had cervical metastasis. All these 6 cases died within one year after operation. One case died of lung metastasis, two cases died of inflammation of lungs. Among 25 patients with cancers, the three-year survival rate was 50.0% (5/10). CONCLUSION: For defects in hypopharynx and cervical esophagus less than 10 cm, silicone rubber tube reconstruction is satisfactory.
Adult↗
[Chemical stability of salmon calcitonin (sCT) analogues in aqueous solution].
Calcitonin is a peptide hormone with 32 amino acids. Natural calcitonins are presumably quite unstable in solution and numerous analogues of calcitonin had been synthesized to improve the stability. In the present paper, we report the investigation of the chemical stability of salmon calcitonin (sCT) analogues [Val1, Ala7]sCT, [Val1, Ala7, Ala30]sCT and [D-Ala30]sCT in aqueous solutions by reversed phase high-performance liquid chromatography (RP-HPLC) and fast atom bombardment mass spectrometry (FAB-MS) methods. The degradation patterns of the sCT analogues showed a marked dependence on pH and temperature. Most of the degradation products in pH 9.0 solution of sCT and its analogues were identified by FAB-MS analysis. Results showed that the sCT analogues are more stable at pH 3.3 and pH 3.7 than at pH 6.0 and pH 9.0. Analogues without disulfide bridge [Val1, Ala7]sCT and [Val1, Ala7, Ala30]sCT showed higher chemical stability than sCT while [D-Ala30]sCT showed lower chemical stability than the native sCT.
Calcitonin↗
[Design and study of carbon fiber tracheal prosthesis].
32 healty adult dogs were selected for this experiment. 10 of them were subjected to the tracheal biomechanics test using indices including the relation between stretcher ratio (lambda) and stress (T), the squeeze stress (delta jy) of medical silk thread on trachea, the side stress (Ts) inducing the tracheal collapse, the functional maximum angle (psi max) of tracheal, and the sever area torsion angle (theta max) of tracheal functional maximum curved. According to the indices measured, two types of tracheal prosthesis were designed, and were made of carbon fiber and silicon. They were the straight tube type tracheal prosthesis and the bifurcate type tracheal prosthesis. The straight tube type tracheal prosthesis was studied with a design of two groups comprising a total of 11 dogs. In the experiment group (n = 6), the outer surface of the tube was not coated with silicon, the average survival period was 379.8 days. In the control group (n = 5), the outer surface of the tube was coated with silicon, the average survival period was 90.4 days. The bifurcate type tracheal prosthesis was studied in 11 dogs, the average survival period was 4.32 days. The main causes of death in the experiment were infection and anastomotic dehiscent.
Animals↗
Overexpression of bcl-2 or bcl-XL fails to inhibit apoptosis mediated by a novel retinoid.
Overexpression of bcl-2 or bcl-XL has been found to inhibit the induction of apoptosis in malignant cells by a large number of agents including a wide variety of chemotherapeutic drugs. CD437 ¿6-[3-(1-adamantyl)-4 hydroxyphenyl]-2-naphthalene carboxylic acid¿ is a novel retinoid that induces apoptosis in a number of malignant cells through a unique mechanism of action. The addition of 1 microM CD437 to HL-60/NEO cells resulted in capase 3 (CPP32) activation and poly(ADP-ribose) polymerase (PARP) cleavage in 3 h whereas in bcl-2- or bcl-XL-overexpressing HL-60 cells CD437 induced CPP32 activation and PARP cleavage in 6 h. Although 50 and 300 nM CD437 were required to induce PARP cleavage in HL-60/NEO and HL-60/bcl-2, HL-60/bcl-XL cells, respectively, maximal apoptosis in both cell lines was achieved utilizing 300 nM CD437. All three cell lines, however, share identical dose-response curves in terms of their growth inhibition, suggesting that CD437-mediated inhibition of growth and induction of apoptosis represent two distinct and separable processes. In addition, CD437 induces GI arrest as well as p21WAFI/CIPI mRNA expression in these cells despite the overexpression of bcl-2 or bcl-XL. CD437 induced mitochondrial instability as indicated by cytochrome c leakage into the cytoplasm in all three cell lines. CD437 also induced growth inhibition and apoptosis of an apoptosis-resistant variant of the HL-60 cell line (HCW-2), which switched expression from bcl-2 to bcl-XL. CD437-mediated apoptosis is not accompanied by downregulation of bcl-2 or bcl-XL or upregulation of bax. The reason for the inability of bcl-2 or bcl-XL overexpression to inhibit CD437-mediated apoptosis is unclear. The ability of CD437 to initiate apoptosis in a spectrum of malignant cells without interference from bcl-2 or bcl-XL overexpression suggests that CD437 may possess significant therapeutic potential in the treatment of malignancy.
Antineoplastic Agents↗
Regulation of water channel activity of aquaporin 1 by arginine vasopressin and atrial natriuretic peptide.
Aquaporin 1 (AQP1), a six-transmembrane domain protein that functions as a water channel, is present in many fluid secreting and absorbing tissues such as kidney, brain, heart, and eye. It is believed that among the five known mammalian aquaporins, kidney aquaporin (AQP2) is the only water channel that is regulated by arginine vasopressin (AVP). The present data suggest that AQP1 may also be regulated by AVP. The application of AVP to Xenopus oocytes injected with AQP1 cRNA increased the membrane permeability to water. In addition, our data reveal that atrial natriuretic peptide (ANP), a peptide hormone that plays an important role in the regulation of body fluid homeostasis, blocks the AQP1-mediated increase in water permeability. Incubation with 8-bromo-cAMP or direct 8-bromo-cAMP injection into oocytes expressing AQP1 cRNA significantly increased membrane permeability to water, suggesting that stimulation of AQP1 activity by AVP may involve a cAMP-dependent mechanism. Regulation of water permeability by AVP and ANP has potential relevance to active water transport in a variety of tissues that express AQP1 including kidney, brain, and eye.
Animals↗
A sequential two-step mechanism for the production of the mature p17:p12 form of caspase-3 in vitro.
The apoptotic cysteine protease, caspase-3, is expressed in cells as an inactive 32-kDa precursor from which 17 kDa (p17) and 12 kDa (p12) subunits of the mature caspase-3 are proteolytically generated during apoptosis. Two amino acid sequences, ESMD downward arrowS (amino acids 25-29) and IETD downward arrowS (amino acids 172-176), in the precursor have been defined as the cleavage sites for the production of the p17 and p12 subunits. Using a cell-free assay system, we demonstrate that the caspase-3 precursor appears to be cleaved first at the IETD downward arrowS site, producing the p12 subunit and a 20-kDa (p20) peptide. Subsequently, the p20 is cleaved at the ESMD downward arrowS site, generating the mature p17 subunit. The cleavage at the IETD downward arrowS site required a protease activity that was selectively inhibited by the peptide, Ac-IETD-CHO (acetyl-IETD-aldehyde), and other protease inhibitors, such as the cowpox viral serine protease inhibitor, CrmA, and N-alpha-tosyl-L-phenylalanine chloromethyl ketone. The protease that catalyzed the cleavage at the ESMD/S site was selectively inhibited by another peptide, Ac-ESMD-CHO (acetyl-ESMD-aldehyde). More interestingly, the caspase-3 inhibitor, Ac-DEVD-CHO, but not the caspase-1 inhibitor, Ac-YVAD-CHO, also selectively inhibited the protease activity that cleaves at the ESMD downward arrowS site. This indicated that the cleavage at the ESMD downward arrowS site was either autocatalytic or that it required a caspase-3-like activity. In summary, we demonstrate that production of the p17:p12 form of caspase-3 is a sequential two-step process and appears to require two distinct enzymatic activities.
Caspase 3↗
Aquaporins and ion conductance.
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Animals↗
Posttranscriptional regulation of collagenase-1 gene expression in synoviocytes by adenosine receptor stimulation.
OBJECTIVE: To characterize the transcriptional and posttranscriptional regulation of collagenase-1 by adenosine receptor stimulation in interleukin-1 (IL-1)-stimulated fibroblast-like synoviocytes (FLS). METHODS: FLS were stimulated with IL-1 and either the nonselective adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA) or the adenylate cyclase activator forskolin. Electrophoretic mobility shift assays were performed to determine AP-1 and cAMP-responsive element binding protein (CREB) activation. Transcriptional activation was determined by transfecting HS68 dermal fibroblasts with a collagenase-chloramphenicol acetyltransferase construct. Finally, collagenase messenger RNA (mRNA) half-life was determined by activating cells in the presence of IL-1, IL-1 + NECA, or IL-1 + forskolin and culturing cells in the presence of actinomycin D. RESULTS: NECA and forskolin had no effect on AP-1 activation, c-jun or c-fos gene expression, or CREB phosphorylation. IL-1 markedly increased collagenase promoter activity, and neither NECA nor forskolin blocked this action. Studies of mRNA half-life showed that both NECA and forskolin decreased the half-life of collagenase mRNA in IL-1-stimulated FLS and HS68 cells. CONCLUSION: The findings of this study demonstrate that NECA and forskolin decrease collagenase gene expression in FLS and dermal fibroblasts due to enhanced mRNA degradation.
Adenosine↗
[Clinical uses of plasma exchange therapy in some diseases].
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Adult↗