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Biomedical subjects

Q He

Publications and source records attributed to Q He.

At least 55 records · Page 3Linked to original sources
PubMed2001

Gender-related differences in subacute fumonisin B1 hepatotoxicity in BALB/c mice.

Fumonisin B1 (FB1), a potent mycotoxin prevalent in corn, is a carcinogen and causative agent of various animal diseases. Species and sex variations to chronic FB1 toxicity have been reported. Free sphingoid bases and cytokine levels are the two major biochemical alterations of FB1 in vivo and may explain any sex differences in FB1 toxicity. Male and female BALB/c mice (5/group) were injected subcutaneously with either saline vehicle or 2.25 mg/kg/day of FB1 for 5 days. One day after the last injection females showed a greater increase in circulating alanine aminotransferase and greater number of apoptotic cells in liver after FB1 treatment than males, indicating greater hepatotoxicity. Peripheral leukocytic counts, including neutrophils, were increased in females only after FB1 treatment. The increased toxicity in females correlated with a greater increase of sphinganine and sphingosine levels in liver after FB1 treatment compared to males. No sex differences in kidney sphinganine or sphingosine levels were observed after FB1 treatment. Previously we have shown the induction of tumor necrosis factor alpha (TNFalpha) in FB1-induced hepatotoxicity. While in males FB1 treatment caused increased expression of TNFalpha, interleukin (IL)-12 p40, interferon gamma (IFNgamma), IL-1beta, IL-6 and IL-10, females showed an increased expression of IL-6 only, and a downward modulation of IFNgamma, indicating gender differences in cytokine pathways in liver activated by FB1. The basal expression of TNFalpha, IL-12 p40, IL-1beta and IFNgamma in liver of females was higher compared to males. Gender differences in alterations of free sphingoid bases and cytokine modulation after FB1 treatment suggest their possible involvement in sex-dependent differential hepatotoxicity in mice.

Alanine Transaminase↗
PubMed2001

Fumonisin-induced tumor necrosis factor-alpha expression in a porcine kidney cell line is independent of sphingoid base accumulation induced by ceramide synthase inhibition.

Previous studies have shown that fumonisin B1 (FB1) inhibits ceramide synthase, resulting in accumulation of free sphinganine and sphingosine. Tumor necrosis factor-alpha (TNFalpha) plays an important role in FB1 toxicity and the expression of TNFalpha mRNA in liver and kidney is increased following FB1 exposure in mice. The objective of the current study was to investigate whether these two events (sphingoid bases accumulation and TNFalpha induction) are dependent on each other. An increase in expression of TNFalpha mRNA was detected in LLC-PK1 cells as early as 4 h after FB1 treatment but decreased to the control levels after 8 h. A positive linear correlation was observed between the expression of TNFalpha mRNA and FB1 concentration. Increases of intracellular sphingoid bases were also detected after 4 h of FB1 treatment and progressively increased until 24 h. Exposure of the cells to sphinganine or sphingosine did not significantly alter the expression of TNFalpha. Inhibition of sphingoid base biosynthesis by ISP-1, a specific inhibitor of serine palmitoyltransferase, the first enzyme in de novo sphingolipid biosynthesis, efficiently blocked the accumulation of free sphingoid bases in response to FB1, but it did not prevent the induction of TNFalpha expression. Results indicate that FB1-induced increase in TNFalpha expression is independent of sphingoid base accumulation-induced by ceramide synthase inhibition in LLC-PK1 cells.

Acyltransferases↗
PubMed2001

Laser-induced photo-cross-linking of cisplatin-modified DNA to HMG-domain proteins.

Laser-induced photo-cross-linking was investigated for DNA, modified with cisplatin at specific sites, bound to structure-specific recognition domains of proteins in the high-mobility group (HMG) class. The efficiency of photo-cross-linking depends on the wavelength and power of the laser, the nature of the protein domain, and the oligodeoxyribonucleotide sequences flanking the platinated site. Introduction of 5-iodouridine at thymine sites of the oligodeoxyribonucleotide as an additional photoreactive group did not increase the photo-cross-linking yield. Formation of platinum-mediated DNA-DNA interstrand cross-linking observed previously upon irradiation with 302 nm light [Kane, S. A., and Lippard, S. J. (1996) Biochemistry 35, 2180-2188] was significantly reduced with laser irradiation. HMG1 domain B is superior to domain A for platinum-mediated photo-cross-linking, a result attributed to the different positioning of the proteins with respect to the platinum adduct and the greater ability of domain B to access photolabilized platinum in the major groove. Studies with proteins containing specifically mutated amino acids, and with DNA probes in which the sequences flanking the platinum cross-link site were varied, suggest that the most effective photo-cross-linking occurs for protein domains bound symmetrically and flexibly to cisplatin-modified DNA. The thermodynamic equilibrium between the protein-platinated DNA complex and its components, revealed in gel electrophoretic mobility shift assays (EMSAs), is significantly shifted to the right upon irreversible photo-cross-linking. Thus, only upon photo-cross-linking can the interaction of cisplatin-DNA 1,3-intrastrand d(GpTpG) or interstrand cross-links with HMG1 domain B protein be detected. Photo-cross-linking is thus an effective tool for investigating the interaction of cisplatin-modified DNA with damage-recognition proteins under heterogeneous conditions such those in cell extracts or living cells.

Base Pairing↗
PubMed2001

Childhood narcolepsy in North China.

STUDY OBJECTIVES: The purpose is to report the results of an effort to diagnose children with narcolepsy in a pediatric referral clinic. DESIGN: Between September 1998 and December 1999, a program was implemented to emphasize recognition of childhood narcolepsy. Patients underwent brain computed tomography (CT) scan and magnetic resonance imaging (MRI) testing. All children received a MSLT test following a routine night's sleep, and serological HLA typing for HLA DR2. Three who reported occasional snoring also underwent nocturnal PSG prior to the MSLT. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: 29 (21 male, 8 female) children were identified with sleepiness and cataplexy. There was no evidence for brain functional or structural disease or for drug use. Sleep paralysis was elicited in 41%; hypnagogic hallucinations, in 59%. Psychosocial problems including emotional irritability and social isolation were present in 93% of the patients. Mean sleep latency on MSLT was 2.0+/-1.3 minutes; sleep-onset rapid eye movement (SOREM) occurred during 2/5 naps in 28 of 29 patients and 3/5 in 26/29 patients. The average number and latency of SOREM episodes were 4.2+/-0.9 episodes and 4.0+/-1.7 minutes, respectively. In those with snoring, a nocturnal PSG did not disclose sleep apneas/hypopneas. All patients but one were HLA DR2 positive. The estimated clinic incidence was 0.04%. CONCLUSIONS: A program for recognition in a referral neurology clinic combined with an availability of the MSLT and HLA testing resulted in the new identification in North China of a number of children with narcolepsy syndromes.

Adolescent↗
PubMed2001

[Breath drive response of COPD patients with hypercapnic respiratory failure and their families].

OBJECTIVE: To investigate the breath drive response of COPD patients and their offspring and to analyze the potential heredity. METHODS: P(0.1) and ventilatory response to hypoxia (DeltaV(E)/DeltaSaO(2)), P(0.1) response to hypoxia (DeltaP(0.1)/DeltaSaO(2)), P(0.1) response to hypercapnia (DeltaP(0.1)/DeltaP(ET)CO(2)DeltaV(E)/P(ET)CO(2)) and ventilatory response to hypercapnia (DeltaV(E)/P(ET)CO(2)) were measured in 6 COPD patients with type II respiratory failure and in 21 of their normal adult offspring. RESULTS: (1) P(0.1) was remarkably higher among all of the COPD patients than among their offspring and normal controls. The hypoxia response (DeltaP(0.1)/DeltaSaO(2)) and DeltaP(0.1)/DeltaP(ET)CO(2) were significantly decreased among the COPD patients (P < 0.05). (2) The hypoxia response was low among 10 of the offspring of COPD patients, and was normal among the other 11. (3) The ventilatory response to hypercapnia (DeltaV(E)/DeltaP(ET)CO(2)) was significantly decreased among the COPD patients, and varied greatly among their offspring. CONCLUSION: (1) The depression of respiratory responses to hypoxia and hypercapnia may be the reason of type II respiratory failure. (2) The depression of hypoxia response may be influenced by genetic factors.

Adult↗
PubMed2001

Involvement of caspases in 4-hydroxy-alkenal-induced apoptosis in human leukemic cells.

4-Hydroxynonenal (HNE), a reactive and cytotoxic end-product of lipid peroxidation, has been suggested to be a key mediator of oxidative stress-induced cell death and in various cell types has been shown to induce apoptosis. We have demonstrated that HNE, at micromolar concentrations, induces dose- and time-dependent apoptosis in a leukemic cell line (CEM-C7). Interestingly, much higher concentrations of HNE (> 15-fold) were required to induce apoptosis in leukocytes obtained from normal individuals. We also demonstrate that HNE causes a decrease in clonogenicity of CEM-C7 cells. Furthermore, our data characterize the caspase cascade involved in HNE-induced apoptosis in CEM-C7 cells. Using specific fluorogenic substrates and irreversible peptide inhibitors, we demonstrate that caspase 2, caspase 3, and caspase 8 are involved in HNE-induced apoptosis, and that caspase 2 is the first initiator caspase that activates the executioner caspase 3, either directly or via activation of caspase 8. Our studies also suggest the involvement of another executioner caspase, which appears to be similar to caspase 8 but not caspases 2 and 3, in its specificity. The demonstration of decreased clonogenicity by HNE in the leukemic cells, and their higher susceptibility to HNE-induced apoptosis as compared to the normal cells, suggests that such compounds may have potential for leukemia chemotherapy.

Aldehydes↗
PubMed2001

Decreased fumonisin hepatotoxicity in mice with a targeted deletion of tumor necrosis factor receptor 1.

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides and related fungi infests corn and other cereals, and causes a variety of toxic effects in different mammalian species. Hepatotoxicity is a common toxic response in most species. The cellular responses of FB1 involve inhibition of ceramide synthase leading to accumulation of free sphingoid bases and a corresponding induction of tumor necrosis factor alpha (TNFalpha). We recently reported that FB1 hepatotoxicity was considerably reduced in a mouse strain lacking tumor necrosis factor receptor 2 (TNFR2 or TNFR1b). To further investigate the relative contribution of the two TNFalpha receptors (TNFR1 and TNFR2 or P55 and P75 receptors) we evaluated the hepatotoxicity of FB1 in male C57BL/6J mice (WT) and a corresponding TNFR1 knockout (TNFRKO) strain, genetically modified by a targeted deletion of this receptor. The hepatotoxic effects of five daily injections of 2.25 mg/kg per day of FB1 were observed in WT but were reduced in TNFRKO, evidenced by the microscopic evaluation of the liver and increased concentrations of circulating alanine aminotransferase and aspartate aminotransferase. FB1 induced the expression of TNFalpha, and similar increases in free sphinganine and sphingosine in livers of both WT and TNFRKO mice. Results indicated that both P55 and P75 receptors are required for FB1-induced hepatotoxicity and TNFalpha plays an important role in such response in mouse liver.

Animals↗
PubMed2001

The high light-inducible polypeptides in Synechocystis PCC6803. Expression and function in high light.

There are five Synechocystis PCC6803 genes encoding polypeptides with similarity to the Lhc polypeptides of plants. Four of the polypeptides, designated HliA-D (Dolganov, N. A. M., Bhaya, D., and Grossman, A. R. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 636-640) (corresponding to ScpC, ScpD, ScpB, and ScpE in Funk, C., and Vermaas, W. (1999) Biochemistry 38, 9397-9404) contain a single transmembrane domain. The fifth polypeptide (HemH) represents a fusion between a ferrochelatase and an Hli-like polypeptide. By using an epitope tag to identify specifically the different Hli polypeptides, the accumulation of each (excluding HemH) was examined under various environmental conditions. The levels of all of the Hli polypeptides were elevated in high light and during nitrogen limitation, whereas HliA, HliB, and HliC also accumulated to high levels following exposure to sulfur deprivation and low temperature. The temporal pattern of accumulation was significantly different among the different Hli polypeptides. HliC rapidly accumulated in high light, and its level remained high for at least 24 h. HliA and HliB also accumulated rapidly, but their levels began to decline 9-12 h following the imposition of high light. HliD was transiently expressed in high light and was not detected 24 h after the initiation of high light exposure. These results demonstrate that there is specificity to the accumulation of the Hli polypeptides under a diverse range of environmental conditions. Furthermore, mutants for the individual and combinations of the hli genes were evaluated for their fitness to grow in high light. Although all of the mutants grew as fast as wild-type cells in low light, strains inactivated for hliA or hliC/hliD were unable to compete with wild-type cells during co-cultivation in high light. A mutant lacking all four hli genes gradually lost its photosynthesis capacity and died in high light. Hence, the Hli polypeptides are critical for survival when Synechocystis PCC6803 is absorbing excess excitation energy and may allow the cells to cope more effectively with the production of reactive oxygen species.

Amino Acid Sequence↗
PubMed2001

Convection compensated electrophoretic NMR.

A novel method of convection compensated ENMR (CC-ENMR) has been developed to detect electrophoretic motion of ionic species in the presence of bulk solution convection. This was accomplished using a gradient moment nulling technique to remove spectral artifacts from heat-induced convection and using the polarity switch of the applied electric field to retain spin phase modulations due to electrophoretic flow. Experiments were carried out with a mixture of 100 mM L-aspartic acid and 100 mM 4,9-dioxa-1,12-dodecanediamine to demonstrate this new method of ENMR. CC-ENMR enhances our previously developed capillary array ENMR (CA-ENMR) in solving the convection problem. The combined CA- and CC-ENMR approach strengthens the potential of multidimensional ENMR in simultaneous structural determination of coexisting proteins and protein conformations in biological buffer solutions of high ionic strength. Structural mapping of interacting proteins during biochemical reactions becomes possible in the future using ENMR techniques, which may have a profound impact on the understanding of biological events, including protein folding, genetic control, and signal transduction in general.

Alkanes↗
PubMed2001

Effects of DL111-IT or combined with RU486 on uterine polyamines biosynthesis in rats during early gestation.

DL111-IT, a non-hormonal contragestional agent, revealed synergistic effects in combination with mifepristone (RU486) in some species. The present study was undertaken to clarify the role of DL111-IT when used alone or plus RU486 on uterine polyamines biosynthesis, histologic alteration of decidual cells, and antifertility activity in rats. The levels of polyamines in pregnant rat uterus were determined by formed benzoyl chloride derivatives of polyamines for RP-HPLC. The results showed that all the treated groups including DL111-IT 2.8 mg. kg(-1). d(-1), RU486 3.0 mg. kg(-1). d(-1), and DL111-IT 0.56 mg. kg(-1). d(-1) plus RU486 0.6 mg. kg(-1). d(-1) caused 100% early pregnancy arrest. Uterine putrescine, spermidine, and spermine levels in comparison with vehicle control were declined significantly from d7 of gestation (1 day after treatment) to d9 or d14 (3 days or 8 days after treatment) by Duncan's multiple range test, and accompanied by histologic alterations, edema, degeneration and dissolution of decidual cells with nuclei indefinite in appearance on d8 of gestation (2 days after treatment). The combined administration at lower doses caused the most injury. The data verified that the decrease in uterine polyamine levels and subsequent decidual cells injuries were the critical role of early pregnancy arrest induced by DL111-IT or RU486. The two compounds used in combination with lower dosages revealed greatly synergistic effects.

Abortifacient Agents, Nonsteroidal↗
PubMed2001

The effects and mechanisms of a novel 2-aminosteroid on murine WEHI-3B leukemia cells in vitro and in vivo.

To evaluate the effects of a novel 2-aminosteroid, 2-(4'-methyl-1'-piperazinyl)-3alpha-hydroxyl-5alpha-androstane-17-one (KH), on in vitro murine WEHI-3B leukemia cells, semisolid colony culture, MTT assay, morphological examination, NBT reduction, NSAE test and ACP assay were used to determine proliferation and differentiation. It was found that the growth of leukemia cells in colony and liquid cultures was inhibited by KH (10(-8)-10(-4) mol/l) after treatment for 7 days. The percentages of NBT and NSAE positive cells were 71.17 and 79.25%, respectively, after treatment with KH (10(-8)-10(-6) mol/l) for 5 days. The morphology of treated leukemia cells was identified to be macrophage-like and these cells acquired significant ACP activities. It was indicated that the ACP enzyme activities were increased as high as two and three times of the control, respectively, after treatment with 10(-8) or 10(-5) mol/l KH for 6 days. It was also indicated by DNA fragmentation in gel electrophoresis that WEHI-3B cells were induced toward apoptosis by KH (10(-8)-10(-4) mol/l) when checked at day 5. The c-myc mRNA expressions in WEHI-3B cells were decreased by 58.7% after treatment with KH (10(-8) mol/l) for 5 days. Therefore, it is first reported here that KH, a novel 2-aminosteroid, could suppress proliferation and induce differentiation of WEHI-3B leukemia cells. These differentiated cells were mature macrophage-like cells and showed characteristics of functional phagocytes acquired with acid phosphatase activity. The mechanisms underlying the above effects involved the apoptosis of WEHI-3B leukemia cells and the down-regulation of c-myc oncogene expression. It is also shown that the counts of immature granulocytes and monocytes were significantly decreased in both peripheral blood and bone marrow of BALB/c leukemia mice after KH was administrated per os for 7 consecutive days with four doses (5, 10, 15 or 20 mg/kg day), respectively. It is also observed that the enlarged spleens in leukemia mice were decreased when compared with the control.

Androstanes↗
PubMed2001

Patterns of open-angle glaucoma in the Barbados Family Study.

OBJECTIVE: To describe the Barbados Family Study of open-angle glaucoma (OAG) and present risk factors for OAG in siblings of study probands. DESIGN: Observational study of families of probands with OAG. PARTICIPANTS: Two hundred thirty probands and 1056 relatives (from 207 families). METHODS: Probands and their family members underwent standardized examinations, including automated perimetry, applanation tonometry, ophthalmologic evaluation, fundus photography, blood pressure, interview, and genotyping. Generalized estimation equation methods were used to evaluate risk factors. MAIN OUTCOME MEASURES: Presence of OAG in the relatives, as defined by both visual field and optic disc findings, after ophthalmologic exclusion of other causes. RESULTS: The median ages of probands and relatives were 68 and 47 years, respectively. In the 207 families, 29% of the probands had one relative with OAG and 10% had two or more relatives affected. Of the 1056 family members, 10% had OAG, 13% had suspect OAG, and 6% had ocular hypertension. One fifth of the 338 siblings had OAG (n = 67); they tended to be older and more often were male. Multivariate comparisons between siblings with and without OAG found that age, higher intraocular pressure (IOP), myopia, and lower diastolic blood pressure-IOP differences were related to OAG, whereas hypertension and diabetes were not. CONCLUSIONS: Based on standardized protocols and examinations, approximately one quarter of the relatives had OAG or suspected OAG, despite their relatively young age. Risk factors for OAG in siblings were similar to risk factors in unrelated individuals. Analyses are ongoing to determine OAG inheritance and to localize potential gene(s) involved.

Adult↗
PubMed2001

Seasonal variations in hydraulic performance of rock-plant filters.

Hydraulic retention time (HRT) may be one of the major factors causing seasonal variations in treatment efficiency of rock-plant filters. Six meso-scale rock-plant filters, three with narrowleaf cattails (Typha augustifolia) and three unplanted, were investigated to evaluate the influence of plant factors on HRT. Tracer studies were conducted during summer, fall, and spring to evaluate seasonal variations in hydraulic performance. Significant evapotranspiration was observed during summer, up to 38.7 mm d(-1), which was five times the corresponding Class A pan evaporation and more than 58% of the applied water. This caused effective HRT to increase by about 50%. Significant gravel expansion also was observed after 2 years of operation. Total bed volume increased up to 21.8%. This increase in bed volume may help maintain porosity and prevent dogging in wetlands. It also caused the subsurface flow pattern to vary from plug flow. High evapotranspiration significantly increased effective HRT in rock-plant filters, which consequently contributed to seasonal variations in treatment performance. Changes in effective HRT should be considered both in process modeling to account for seasonal hydraulic variations and in wetland operations to prevent potential dry-out during warm seasons.

Filtration↗
PubMed2001

Inducible regulation of human brain natriuretic peptide promoter in transgenic mice.

Studies have shown that brain natriuretic peptide (BNP) gene expression is rapidly induced in the infarcted heart and that plasma BNP levels reflect the degree of left ventricular dysfunction. Our previous in vitro work using transiently transfected neonatal rat cardiac myocytes has shown that the human BNP (hBNP) promoter, in particular a region extending from -127 to -40 relative to the start site of transcription, is more active in cardiac myocytes than in fibroblasts. To study tissue-specific and transcriptional regulation of the hBNP gene in vivo, we generated transgenic mice containing the proximal hBNP promoter (-408 to +100) coupled to a luciferase reporter gene. In four lines of transgenic mice, luciferase activity was approximately 33- to 100-fold higher in the heart than in other tissues, including the whole brain. To test whether the transgene responded to a pathophysiological stimulus, we induced infarction by coronary artery ligation. Luciferase activity was fivefold higher in the infarcted region of the left ventricle at 48 h than in sham-operated animals and remained elevated for 4 wk. Endogenous BNP mRNA was similarly increased in the infarcted hearts of a separate group of mice. We conclude that 1) the proximal 408-bp region of the hBNP promoter confers cardiac-specific expression and 2) myocardial infarction activates the proximal hBNP promoter in vivo. These data suggest that we have a valid model for the study of basal and inducible regulation of the hBNP gene in vivo.

Animals↗
PubMed2001

Investigation on cell proliferation with a new antibody against thymidine kinase 1.

The cytosolic thymidine kinase 1 (TK1) is one of the enzymes involved in DNA replication. Based on biochemical studies, TK1 is activated at late G1 of cell cycle, and its activity correlates with the cell proliferation. We have developed a polyclonal anti-TK1 antibody against a synthetic peptide from the C-terminus of human TK1. Using this antibody, here we demonstrate the exclusive location of TK1 in the cytoplasm of cells. Cell cycle dependent TK1 expression was studied by simultaneous fluorescence staining for TK1 and bromodeoxyuridine, by using elutriated cells, and by quantitation of the amount TK1 in relation to the cellular DNA content. TK1, which was strongly expressed in the cells in S+G2 period, raised at late G1 and decreased during mitosis. The amount of TK1 increased three folds from late G1 to G2. TK1 positive cells were demonstrated in areas of proliferation activity of various normal and malignant tissues. The new anti-TK1 antibody works in archival specimens and is a specific marker of cell proliferation.

Animals↗
PubMed2001

Src and Rac mediate endothelin-1 and lysophosphatidic acid stimulation of the human brain natriuretic peptide promoter.

Brain natriuretic peptide (BNP) gene expression accompanies cardiac hypertrophy and heart failure. The vasoconstrictor endothelin-1 (ET) may be involved in the development of these diseases. ET has also been shown to activate phospholipase A(2) (PLA(2)), and the resulting metabolites are important second messengers. We studied how ET and PLA(2) metabolites regulate BNP gene expression. The human BNP (hBNP) promoter (from -1818 to +100) coupled to a luciferase reporter gene was transferred into neonatal ventricular myocytes (NVMs), and luciferase activity was measured as an index of promoter activity. ET induced BNP mRNA in NVMs as assessed by Northern blot. It also stimulated the hBNP promoter, an effect completely inhibited by actinomycin D. To test the involvement of different PLA(2) isoforms, transfected cells were treated with various PLA(2) inhibitors before stimulation with ET. Only Ca(2+)-independent PLA(2) blockade prevented ET-stimulated hBNP promoter activity. The PLA(2) metabolite lysophosphatidic acid (LPA) also activated the hBNP promoter, but arachidonic acid itself did not. ET regulation of the hBNP promoter is pertussis toxin-sensitive. The nonreceptor tyrosine kinase Src and the small GTPase Rac mediate the effects of both ET and LPA in stimulation of the hBNP promoter. We studied the involvement of cis elements in ET-stimulated hBNP promoter activity. Deletion of BNP promoter sequences from -1818 to -408 and from -408 to -40 reduced the effect of ET by 60% and 80%, respectively. Moreover, ET-stimulated luciferase activity was reduced by 50% when the proximal GATA element was mutated. These data suggest that (1) ET activates the hBNP promoter through a transcriptional mechanism; (2) LPA, perhaps generated by iPLA(2), is involved in the effect of ET; (3) Src and Rac mediate ET and LPA stimulation of the hBNP promoter; and (4) ET regulation of the hBNP promoter targets both distal and proximal cis elements.

Animals↗
PubMed2001

Acute pancreatitis signals activation of apoptosis-associated and survival genes in mice.

In experimental models of acute pancreatitis (AP), acinar cell death occurs by both necrosis and programmed cell death or apoptosis. Apoptosis is an active form of cell death associated with a tightly regulated expression of gene products that are either pro- or antiapoptotic. The aim of this study was to characterize pancreatic mRNA levels by Northern blotting analysis of apoptosis-associated genes used during the course of cerulein-induced AP in mice. Histone H3 mRNA levels were also examined as an indicator of cell proliferation. Acinar cell apoptosis was confirmed histologically. The findings show that AP modifies pancreatic mRNA levels of both pro- and antiapoptotic genes simultaneously. Pancreatic bclXL, bax, and p53 mRNA levels increased significantly in a temporal fashion during induction of AP. Pancreatic bcl-2 mRNA levels were unchanged during AP. Pancreatic mRNA levels of insulin-like growth factor-1 (IGF-1), a mitogen and cell survival factor, and its receptor (IGF-1R) also increased in a temporal fashion during induction of AP. In summary, this study indicates that acinar cell death during cerulein-induced AP in mice can occur by the apoptotic pathway. Since factors promoting and antagonistic for cell survival are activated simultaneously, regulation of acinar cell survival appears complex and dynamic during AP.

Acute Disease↗