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Biomedical subjects

A Zhou

Publications and source records attributed to A Zhou.

At least 19 recordsLinked to original sources
PubMed2001

Apo2L/TRAIL and Bcl-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma.

It has been reported that interferons (IFNs) may have antitumor activity in multiple myeloma (MM). The mechanism for their effect on MM, however, remains elusive. This study shows that IFN-alpha and -beta, but not -gamma, induce apoptosis characterized by Annexin V positivity, nuclear fragmentation and condensation, and loss of clonogenicity in 3 MM cell lines (U266, RPMI-8266, and NCI-H929), and in plasma cells from 10 patients with MM. Apo2 ligand (Apo2L, also TRAIL) induction was one of the earliest events following IFN administration in U266 cells. Treatment of these cells with TRAIL, but not with Fas agonistic antibodies, induces apoptosis. Cell death induced by IFNs and Apo2L in U266 cells was partially blocked by a dominant-negative Apo2L receptor, DR5, demonstrating the functional significance of Apo2L induction. This study shows that IFNs activate caspases and the mitochondrial-dependent apoptotic pathway, possibly mediated by Apo2L production. Thus, IFN-alpha and -beta induce cytochrome c release from mitochondria starting at 12 hours, with an amplified release seen at 48 hours. Moreover, Bid cleavage precedes the initial cytochrome c release, whereas the late, amplified cytochrome c release coincides with changes in levels of Bcl-2, Bcl-X(L), and reduction of mitochondrial membrane potential. These results link the Apo2L induction and modulation of Bcl-2 family proteins to mitochondrial dysfunction. Furthermore, IFNs and Apo2L induce cell death of CD38(+)/CD45(-/dim) plasma cells, without significant effect on nonplasma blood cells, in a caspase and Bcl-2 cleavage-dependent manner. These results warrant further clinical studies with IFNs and Apo2L in MM.

Apoptosis↗
PubMed2001

Severe defect in proglucagon processing in islet A-cells of prohormone convertase 2 null mice.

Mice homozygous for a deletion in the gene encoding prohormone convertase 2 (PC2) are generally healthy but have mild hypoglycemia and flat glucose-tolerance curves. Their islets show marked alpha (A)-cell hyperplasia, suggesting a possible defect in glucagon processing (Furuta, M., Yano, H., Zhou, A., Rouille, Y., Holst, J., Carroll, R., Ravazzola, M., Orci, L., Furuta, H., and Steiner, D. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 6646-6651). In this report we have examined the biosynthesis and processing of proglucagon in isolated islets from these mice via pulse-chase labeling and find that proglucagon undergoes essentially no processing in chase periods up to 8 h in duration. Only a small percent of cleavage at the sensitive interdomain site (residues 71 and 72) appears to occur. These observations thus conclusively demonstrate the essentiality of PC2 for the production of glucagon in the islet A-cells. Ultrastructural and immunocytochemical studies indicate the presence of large amounts of proglucagon in atypical appearing secretory granules in the hyperplastic and hypertrophic A-cells, along with morphological evidence of high rates of proglucagon secretion in PC2 null islets. These findings provide strong evidence that active glucagon is required to maintain normal blood glucose levels, counterbalancing the action of insulin at all times.

Animals↗
PubMed2001

The serpin inhibitory mechanism is critically dependent on the length of the reactive center loop.

The recent crystallographic structure of a serpin-protease complex revealed that protease inactivation results from a disruption of the catalytic site architecture caused by the displacement of the catalytic serine. We hypothesize that inhibition depends on the length of the N-terminal portion of the reactive center loop, to which the active serine is covalently attached. To test this, alpha(1)-antitrypsin Pittsburgh variants were prepared with lengthened and shortened reactive center loops. The rates of inhibition of factor Xa and of complex dissociation were measured. The addition of one residue reduced the stability of the complex more than 200,000-fold, and the addition of two residues reduced it by more than 1,000,000-fold, whereas the deletion of one or two residues lowered the efficiency of inhibition and increased the stability of the complex (2-fold). The deletion of more than two residues completely converted the serpin into a substrate. Similar results were obtained for the alpha(1)-antitrypsin variants with thrombin and for PAI-1 and PAI-2 with their common target tissue plasminogen activator. We conclude that the length of the serpin reactive center loop is critical for its mechanism of inhibition and is precisely regulated to balance the efficiency of inhibition and stability of the final complex.

Amino Acid Sequence↗
PubMed2001

A piezoelectric quartz crystal impedance study on Cu(2+)-induced precipitation of bovine serum albumin in aqueous solution.

Piezoelectric quartz crystal impedance (QCI) technique was used for monitoring the Cu(2+)-induced precipitation of bovine serum albumin onto the gold electrode. The critical precipitate concentration of Cu(2+) reflected by the significant decrease in the resonant frequency was estimated to be 9.98 x 10(-5) mol x l(-1), and the saturated adherence of the precipitate on the electrode occurred when the Cu(2+) concentration was greater than 9.79x10(-3) mol x l(-1). The frequency shift in air was about 85.5% of that in liquid, and the Deltaf(0)/DeltaR(1) ratio found in solution was 82.67 Hz Omega(-1), suggesting that the frequency response was predominated by the mass change due to precipitate adherence to the electrode surface. The response of the resonant frequency was analyzed using an equation Deltaf=a(0) + a(1) e(-t/tau(1)) + a(2) e(-t/tau(2)). The relationship between the total a(0) values and the Cu(2+) concentration was discussed.

Animals↗
PubMed2001

Analysis of chromosomal and organellar DNA of somatic hybrids between Triticum aestiuvm and Haynaldia villosa Schur.

Intergeneric somatic hybridization between wheat (cv. Jinan 177) protoplasts that have 24-28 chromosomes and Haynaldia villosa protoplasts containing 11-14 chromosomes was carried out by the polyethylene glycol (PEG) method. A high frequency of hybrid calli and plants were obtained from the fusion products, as revealed by cytological and biochemical techniques and by PCR analysis of 5S rDNA spacer sequences. GISH (genomic in situ hybridization) analysis confirmed the presence of chromosomes from both parents in the hybrid clones and the common occurrence of translocations between them. The RFLP analysis of the organellar DNA using mitochondrion- and chloroplast-specific probes revealed that mitochondria from both parents existed in the cells of hybrid calli and their recombination, whereas chloroplasts segregated and recombined randomly. The gross morphology of hybrid plants resembled that of wheat, but the gross morphology of their ovaries and anthers were intermediate between those of the two parents. The relationship between hybrid plant regeneration and the balance of genetic materials in hybrid clones is discussed.

Blotting, Southern↗
PubMed2001

Application of double-impedance system and cyclic voltammetry to study the adsorption of fullerols (C60(OH)n) on biological peptide-adsorbed gold electrode.

The adsorption of fullerols (C60(OH)n) on glutathione-adsorbed gold electrode was characterized by using double-impedance system, i.e., electrochemical quartz crystal impedance and electrochemical impedance spectroscopy, and cyclic voltammetry. The time courses of piezoelectric parameters were used to reflect the changes of interfacial physical properties, such as mass, density-viscosity, and dielectric constant, during the adsorptions of peptide and fullerols onto electrode. The electrochemical impedance based on the simple equivalent electric network were also simultaneously measured and provided electrochemical interface information, e.g., double-layer capacitance and charge-transfer resistance. It was found that the double-impedance responses were varied with the forms of glutathione. It was also shown that the frequency curves due to the adsorption of oxidized (GSSG) and reduced (GSH) glutathione could be exhibited as different kinetic equations. The heterogeneous charge-transfer rate constants of ferricyanide/ferrocyanide before and after the peptide and fullerols adsorption were determined by CV and EIS methods. The results showed that the proposed method has potential applications in interfacial studies of biomaterials, since these combined techniques have advantages in real time providing multidimensional piezoelectric and electrochemical impedance information.

Adsorption↗
PubMed2001

Altered expression of the neuropeptide-processing enzyme carboxypeptidase E in the rat brain after global ischemia.

Carboxypeptidase E, an exoprotease involved in the processing of bioactive peptides released by a regulated secretory pathway, was identified in a subtractive complementary DNA library derived from an ischemic rat brain by differential screening. In situ hybridization and immunocytochemical analysis showed the presence of carboxypeptidase E messenger RNA and protein in the cerebral cortex, thalamus, striatum, and hippocampus of a healthy rat brain. After 15 minutes of transient global ischemia followed by 8 hours of reperfusion, increased levels of carboxypeptidase E messenger RNA and protein were observed in the hippocampal CA1 and CA3 regions and in the cortex, as detected by Northern and Western blot analyses and in situ hybridization. After extended reperfusion (24 to 72 hours), both carboxypeptidase E messenger RNA and protein levels were decreased. The ischemia-induced changes in carboxypeptidase E expression suggest that this enzyme may play a role in modulating the brain's response to ischemia.

Animals↗
PubMed2001

Gravidity-dependent production of antibodies that inhibit binding of Plasmodium falciparum-infected erythrocytes to placental chondroitin sulfate proteoglycan during pregnancy.

During pregnancy, Plasmodium falciparum-infected erythrocytes sequester in the placenta by adhering to chondroitin 4-sulfate, creating a risk factor for both the mother and the fetus. The primigravidae are at higher risk for placental malaria than the multigravidae. This difference in susceptibility has been attributed to the lack of antibodies that block the adhesion of infected erythrocytes to placental chondroitin 4-sulfate in primigravid women. However, recent results show that many primigravidae at term have antibody levels similar to those of multigravidae, and thus the significance of antiadhesion antibodies in providing protection against malaria during pregnancy remains unclear. In this study, we analyzed plasma samples from women of various gravidities at different gestational stages for antiadhesion antibodies. The majority of women, regardless of gravidity, had similar levels of antibodies at term. Most primigravidae had low levels of or no antiadhesion antibodies prior to ~20 weeks of pregnancy and then produced antibodies. Multigravidae also lacked antibodies until ~12 weeks of pregnancy, but thereafter they efficiently produced antibodies. In pregnant women who had placental infection at term, higher levels of antiadhesion antibodies correlated with lower levels of placental parasitemia. The difference in kinetics of antibody production between primigravidae and multigravidae correlated with the prevalence of malaria in these groups, suggesting that antibodies are produced during pregnancy in response to placental infection. The early onset of efficient antibody response in multigravidae and the delayed production to antibodies in primigravidae appear to account for the gravidity-dependent differential susceptibilities of pregnant women to placental malaria.

Adult↗
PubMed2001

Increased severity of HSV-1 keratitis and mortality in mice lacking the 2-5A-dependent RNase L gene.

PURPOSE: The2',5'-oligoadenylate-dependent RNase L gene functions in the interferon-inducible RNA decay pathway known as the 2-5A system. The purpose of this study was to determine whether the absence of this gene affects the pathogenesis of herpes simplex virus type 1 (HSV-1) ocular infection in the mouse. METHODS: HSV-1 (strain McKrae) was applied bilaterally to unscarified corneas of RNase L-null mice and congenic controls. To evaluate the severity of herpetic keratitis, slit lamp examinations (SLE) were performed every other day for 14 days. To study corneal histology and apoptosis, HSV-1-inoculated RNase-L-null and congenic control mice, as well as mock-inoculated mice (apoptosis negative control), were killed at 6 and 18 hours postinoculation (PI). Uninoculated mice that underwent corneal scarification (apoptosis positive control) were killed 2 hours after scarification. Eyes were dissected and the corneas processed for light and transmission electron microscopy and the TUNEL assay. RESULTS: In comparison with the congenic control mice, RNase L-null mice showed significantly more severe herpetic keratitis (PI day 8, SLE score, mean +/- SEM: 3.27 +/- 0.10 vs. 2.34 +/- 0.06; P: < 0.001) and significantly higher mortality (PI day 14, 70% vs. 20%; P: < 0.001). Few apoptotic cells were seen in HSV-1-infected RNase L-null mice, although DNA fragmentation consistent with apoptosis was detected in the corneas of congenic control mice 6 and 18 hours after HSV-1 inoculation and in uninfected mice with scarified corneas. Signs of apoptosis were not present in the mock-infected corneas. Electron microscopic evidence of keratocytic apoptosis was detected only in the uninfected scarified corneas and the HSV-1-infected congenic control corneas. CONCLUSIONS: The increased severity of ocular disease and increased mortality in the RNase L-null mice provides evidence, for the first time, that the 2-5A system contributes to protection during ocular herpetic infection. The reduced frequency of apoptosis in these mice suggests that one possible mechanism for this protective effect could be the induction of apoptosis in corneal cells as a means of reducing the spread of infectious virus.

Animals↗
PubMed2001

The conformational basis of thrombosis.

Antithrombin readily undergoes a spontaneous transition from its active five-stranded form to a six-stranded inactive latent form. The recognition of this change in plasma has been obscured by the immediate linkage of newly formed latent antithrombin to a molecule of active antithrombin to give a dimer with an electrophoretic mobility readily confused with that of native active antithrombin. A new micromethod now allows unequivocal identification of latent antithrombin in whole plasma. This shows that at 37 degrees C some 10% of plasma antithrombin is converted to the latent form in 24 h. The rate of conversion is greatly accelerated at increased temperatures, as occurs in the pasteurisation of plasma concentrates that should now be checked for efficacy. But increased transition also occurs in the plasma at the slightly increased temperatures that accompany incidental infections. This is of particular significance if there is a conformationally unstable variant of antithrombin; here fever can provoke a sudden transition with the onset of a characteristically severe episode of thromboembolism. Such variants are not rare and include those previously classified as pleiotropic. The precise structural pathway, now known with antithrombin, provides a model of the changes occurring in other conformational diseases, including Alzheimer's and the prion dementias.

Antithrombins↗
PubMed2001

The role of hypertension-related gene in aortic vascular smooth muscle cells from mice and rats.

OBJECTIVE: To study the role of hypertension-related gene (HRG-1) in cardiovascular disease. METHODS: The expression of HRG-1 was analyzed with RT-PCR and Northern blotting. Vascular smooth muscle cell (VSMC) proliferation was measured with 3H-TdR incorporation and was confirmed with histological analysis. RESULTS: Northern blot analysis showed that HRG-1 mRNA was expressed not only in VSMC, but also in various rat tissues (heart, brain, lung, kidney, and liver). In addition, the expression of HRG-1 mRNA in heart, brain, kidney and liver of spontaneously hypertensive rat (SHR) was lower than that in the same tissues of Wistar-Kyotorat (WKY). Semi-quantitative RT-PCR and histological analysis showed that the expression of HRG-1 mRNA in ApoE-knockout mice and in animal models of restenosis was decreased and neointimal formation was observed in both models. ET, AII, and IL-1 stimulating VSMC proliferation reduced the expression of HRG-1 mRNA of VSMC. Atrial natriuretic factor (ANF), calcitonin gene-related peptide and adrenomedullin, inhibited VSMC proliferation and elevated the expression of HRG-1 mRNA. These effects could be blocked or attenuated by their corresponding antagonists or antibodies. CONCLUSION: HRG-1 is a gene related to VSMC proliferation. It may play an important role in several occlusive cardiovascular diseases including atherosclerosis, restenosis and hypertension.

Animals↗
PubMed2001

Percutaneous balloon aortic valvuloplasty in the treatment of congenital valvular aortic stenosis in children.

OBJECTIVE: To assess the effect of the balloon valvuloplasty for for congenital valvular aortic stenosis (AS) in children. METHODS: A total of 27 (mean age 6.09 years) children with AS accepted the treatment of percutaneous balloon aortic valvuloplasty (PBAV). The ratios of balloon/valve were 0.95 +/- 0.08 for 19 cases of typical AS and 1.00 +/- 0.11 for 8 cases of hypoplastic AS. The patients were evaluated by the gradients across aortic valves in pre- and post-PBAV and by echocardiogram during the follow-up period. RESULTS: Fifteen of 19 (78.9%) cases of typical AS had a better outcome and the gradient of the remaining 4 cases (26.7%) had increased after follow-up (delta P > 50 mm Hg). Four of 8 (50.0%) cases of hypoplastic AS had satisfactory responses and the gradient of the remaining 3 cases (75.0%) rose. There was no moderate to severe aortic insufficiency (AI). CONCLUSION: The balloon aortic valvuloplasty provides safe and significant hemodynamic and clinical improvement in pediatric patients. The outcome of PBAV for typical AS is better than for hypoplastic AS.

Adolescent↗
PubMed2001

Percutaneous balloon angioplasty of coarctation of the aorta in children: 12-year follow-up results.

OBJECTIVE: To evaluate the efficiency of percutaneous balloon angioplasty of coarctation of the aorta in children and discuss its risk factors that can lead to poor long-term results. METHODS: From September 1987 to August 1999, 24 patients underwent 27 balloon angioplasty procedures for native or recurrent coarctation of the aorta at our institution. There were 19 patients with discrete (membranous) coarctation, 4 patients with long-segment and aortic arch hypoplasia, and 1 patient with postoperative recurrence. The balloon diameter was chosen not to exceed the diameter of the aorta proximal to the stenotic site (11.06 +/- 2.80 mm vs 11.78 +/- 3.18 mm), with the chosen diameter two to four times that of the stenotic segment (2.57 +/- 0.68 times). The patients have been followed up for half to twelve years (mean 6.2 +/- 2.8 years). Satisfactory result was defined as a reduction in the pressure gradient across the site of coarctation to < or = 20 mm Hg. RESULTS: The systolic pressure gradient across the coarctation site decreased from 48.17 +/- 14.68 mm Hg to 14.96 +/- 13.12 mm Hg (P < 0.01) and the diameter of the coarctation site increased from 4.66 +/- 2.43 mm to 8.80 +/- 3.32 mm (P < 0.01). Immediate satisfactory results were obtained in 19 patients (79%). Of the 5 patients with unsatisfactory results, 4 had aortic arch hypoplasia and 1 had membranous coarctation. Of the 19 patients with satisfactory results, 18 patients had membranous coarctation and 1 patient had recurrent postoperative coarctation. No aneurysm and other complications had occurred in any patients at the follow-ups. CONCLUSION: Percutaneous balloon angioplasty is an effective treatment alternative to surgery in most patients with recurrent postoperative or native membranous coarctation of the aorta. It should not be recommended for the coarctation of aortic arch hypoplasia.

Adolescent↗
PubMed2001

All-trans retinoic acid in pulmonary vascular structural remodeling in rats with pulmonary hypertension induced by monocrotaline.

OBJECTIVE: To determine whether all-trans retinoic acid (atRA) exerts an inhibitory effect on rats with pulmonary hypertension induced by monocrotaline. METHODS: All rats were given a single subcutaneous injection of either monocrotaline (60 mg/kg) or saline. Monocrotaline-injected rats received either atRA (30 mg.kg-1.day-1) or saline through oral-gastro intubation. On Days 7, 14, 21, and 28 respectively after monocrotaline injection, cardiovascular catheters were inserted to examine the mean pulmonary artery pressure of rats in each group. Meanwhile, the matrix metalloproteinase-1 (MMP-1) mRNA expression and hydroxyproline content in the main pulmonary artery were determined by RT-PCR and chromometry, respectively. RESULTS: The mean pulmonary artery pressure of rats in the model group increased significantly on day 21 and reached a peak on Day 28 compared with the control group (25.7 +/- 4.3 mm Hg vs 15.1 +/- 1.5 mm Hg and 38.5 +/- 6.4 mm Hg vs 16.4 +/- 2.0 mm Hg, P < 0.01). MMP-1 mRNA overexpression was present on Day 14 (0.72 +/- 0.15 vs 0.39 +/- 0.08, P < 0.01) and was rapidly down-regulated on Day 21 and 28 compared with Day 14, but was still higher than that in the control. The hydroxyoroline content of the main pulmonary artery dropped significantly on Day 14 (4.01 +/- 1.13 micrograms/mg vs 5.10 +/- 0.91 micrograms/mg, P < 0.05) and increased significantly on Days 21 and 28 compared with the control. atRA inhibited the MMP-1 mRNA overexpression from Day 14 to Day 28 and reduced the hydroxyproline content (5.59 +/- 0.70 micrograms/mg vs 7.96 +/- 1.13 micrograms/mg and 7.77 +/- 0.96 micrograms/mg vs 9.93 +/- 1.27 micrograms/mg, P < 0.01) and the mean pulmonary artery pressure compared with the model group (19.6 +/- 3.2 mm Hg vs 25.7 +/- 4.3 mm Hg and 26.3 +/- 4.6 mm Hg vs 38.5 +/- 6.4 mm Hg, P < 0.01). CONCLUSION: atRA inhibits MMP-1 overexpression and the accumulation of collagen, which might elicit favorable geometric remodeling in rat pulmonary hypertension induced by monocrotaline.

Animals↗
PubMed2001

[Seroepidemiological analysis of characteristic of hepatitis B virus in children after vaccination in Ningbo].

OBJECTIVE: To understand the immunity of children in Ningbo after hepatitis B vaccination for seven years and to explore the best time for booster. METHODS: One thousand nine hundred and twenty serum samples from children born in 1982 - 1995 were tested for anti-HBs and HBsAg, using RIA. RESULTS: (1) HBsAg positive rate (2.66%) was lower in vaccinated children born in 1992 - 1995 than those unvaccinated (10.92%) born in 1982 - 1995. HBsAg positive rate had a drop of 75.71% (chi(2) = 22.91, P < 0.0001). (2) Anti-HBs positive rates (65.95%) in vaccinated children was much higher than that in unvaccinated children (41.03%) (chi(2) = 113.67, P < 0.0001). (3) It also showed that children's positive rate of HBsAg increased and anti-HBs dropped after 5 - 7 years of vaccination. CONCLUSION: After immunization of hepatitis B vaccine for 7 years, high immunity and low infection rate of HB in children it appeared in Ningbo. However it is necessary to further study the reason causing the increase of HBsAg positive rate and/or deerease of anti-HBs positive rate, and the suitable time frame of boostering, after 4 or 5 years of primary vaccination.

China↗
PubMed2001

[Human papilloma virus infection and expression of p16 protein in laryngeal papilloma and laryngeal carcinoma].

OBJECTIVE: To evaluate the role of human papilloma virus (HPV) infection and inactivation of p16 gene in laryngeal papilloma (LP) and laryngeal squamous cell carcinoma (LC). METHODS: HPV consensus primers direct in situ polymerase chain reaction (ISPCR) and immunohistochemical method were applied to detect the presence of HPV genomes (1, 6, 8, 11, 13, 16, 18, 30, 31, 32, 33, 45, 51) and the expression of p16 protein respectively in 93 cases of formalin-fixed, paraffin-imbedded specimens, which contained 46 cases of LPs [adult-onset laryngeal papilloma (ALP) 21, juvenile-onset laryngeal papilloma (JLP)25], 26 cases of LCs, 6 cases of normal tissues adjacent to carcinoma, and 15 cases of vocal noduli. RESULTS: (1) The difference of positive rates of HPV-DNA in JLP group (84%, 21/25) and other groups were statistically significant (chi 2 test, P < 0.05). The difference of positive rates of HPV-DNA in ALPs(38.1%, 8/21), in LCs(19.2%, 5/26), in vocal noduli(0%, 0/15), and in normal tissues adjacent to carcinoma(0%, 0/6) were not significant statistically (chi 2 test or Fisher's exact probability test, P > 0.05). (2) The positive rates of expression of p16 protein in ALP group(57.1%, 12/21) and LC group(38.5%, 10/26) were significantly lower than that in vocal nodule group(93.3%, 14/15), in JLP group(88%, 22/25), and in normal tissues adjacent to carcinoma group (100%, 6/6) (chi 2 test or Fisher's exact probability test, P > 0.05). There were no significant differences of positive rates of expression of p16 protein between ALP group and LC group, and between JLP group and vocal nodule group (chi 2 test, P > 0.05). (3) In LPs, the difference of positive rates of p16 protein expression between HPV positive cases and HPV negative cases was significant statistically (chi 2 test, P < 0.05). In LCs, there was no difference in p16 protein expression rate between the two teams(Fisher exact probability test, P > 0.05). CONCLUSION: The pathogenesis of JLP is closely associated with HPV infection and not associated with the inactivation of p16 gene. Conversely, the pathogenesis of ALP and LC is associated with the inactivation of p16 gene and not associated with the HPV infection.

Adult↗
PubMed2000

Polymerization of plasminogen activator inhibitor-1.

The activity of the serine proteinase inhibitor (serpin) plasminogen activator inhibitor-1 (PAI-1) is controlled by the intramolecular incorporation of the reactive loop into beta-sheet A with the generation of an inactive latent species. Other members of the serpin superfamily can be pathologically inactivated by intermolecular linkage between the reactive loop of one molecule and beta-sheet A of a second to form chains of polymers associated with diverse diseases. It has long been believed that PAI-1 is unique among active serpins in that it does not form polymers. We show here that recombinant native and latent PAI-1 spontaneously form polymers in vitro at low pH although with distinctly different electrophoretic patterns of polymerization. The polymers of both the native and latent species differ from the typical loop-A-sheet polymers of other serpins in that they readily dissociate back to their original monomeric form. The findings with PAI-1 are compatible with different mechanisms of linkage, each involving beta-strand addition of the reactive loop to s7A in native PAI-1 and to s1C in latent PAI-1. Glycosylated native and latent PAI-1 can also form polymers under similar conditions, which may be of in vivo importance in the low pH environment of the platelet.

Amino Acid Sequence↗