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Biomedical subjects

G Assmann

Publications and source records attributed to G Assmann.

At least 127 records · Page 7Linked to original sources
PubMed1998

Differential effects of lovastatin on the trafficking of endogenous and lipoprotein-derived cholesterol in human monocyte-derived macrophages.

Lovastatin has been shown to reduce cholesterol esterification in cholesterol-loaded human macrophages. Surprisingly, in nonloaded macrophages, lovastatin produces the opposite effect, lowering free cholesterol and increasing cholesteryl ester levels, as measured by high-performance liquid chromatography. In cholesterol-loaded cells, lovastatin reduced the cholesteryl esters of unsaturated but not those of saturated fatty acids. In nonloaded cells, by contrast, the cholesteryl esters of unsaturated fatty acids tended to increase after lovastatin treatment. Total (free plus esterified) cellular cholesterol content in nonloaded cells fell by 18% with 12-micromol/L lovastatin treatment but did not change in cholesterol-loaded cells. Lovastatin had no effect on the binding or uptake of acetylated low density lipoprotein, acyl coenzyme A:cholesterol acyltransferase (ACAT) activity, the secretion of [3H]cholesterol into the medium, or lysosomal hydrolysis of cholesteryl esters. Apolipoprotein (apo) E mRNA levels increased but apoE secretion into the medium decreased with lovastatin treatment in both cholesterol-loaded and nonloaded cells. Cholesterol of exogenous origin has been shown to pass via the cell membrane before its esterification by ACAT. We postulate that this is not the case for endogenous cholesterol, which may have direct access to ACAT. Our findings therefore suggest that lovastatin hinders the delivery of intracellular cholesterol to the plasma membrane, resulting in increased free cholesterol and lower levels of cholesteryl ester in cholesterol-loaded cells. In nonloaded cells, virtually all cholesterol is of endogenous origin and is normally translocated to the cell membrane. Lovastatin prevents this process, thus shunting newly synthesized cholesterol toward esterification and leading to an increase in the concentration of cholesteryl esters, even in the face of a drop in total and free cholesterol levels. Intracellular apoE may play a role in this process.

Analysis of Variance↗
PubMed1998

Factor V Leiden mutation is a risk factor for cerebral venous thrombosis: a case-control study of 55 patients.

BACKGROUND AND PURPOSE: Different coagulation disorders have been associated with cerebral venous thrombosis (CVT). Until now, fewer than 50 patients have been reported with CVT and the factor V Leiden (FVL) mutation. Although the prevalence of FVL-positive patients with CVT ranged from 10% to 25%, it was as low as 0.5% to 3% in the control groups. Most other studies had not systematically searched for concomitant risk factors or previous thromboembolic events. To better define the relevance of the FVL mutation in conjunction with additional risk factors in CVT, we conducted the present case-control study. METHODS: Fifty-five patients with CVT were compared with 272 healthy controls. A standardized interview regarding established risk factors for venous thrombosis and the patients' and their families' histories for thromboembolic events was performed. The presence of the FVL mutation was determined by polymerase chain reaction on DNA obtained from peripheral blood leukocytes. RESULTS: Of 55 patients, 8 (14.5%) were heterozygous for the FVL mutation compared with 17 of 272 controls (6.25%). The relative risk for the presence of FVL was 2.55 (95% confidence interval, 1.04 to 6.26; P=0.04). Additional risk factors for CVT were frequently found in both the presence and absence of FVL. Recurrence of venous thromboembolic events was more frequent in patients with the FVL mutation (5 of 8 patients, 62.5%) than in those without this anomaly (8 of 47 patients, 17%; P<0.005). CONCLUSIONS: Our study confirms the FVL mutation as the most relevant hereditary risk factor for CVT. Coexisting risk factors are usually involved in the initiation of CVT. Patients with the FVL mutation are at an increased risk for recurrent venous thrombosis.

Adolescent↗
PubMed1998

Incidence and risk factors for stroke in an occupational cohort: the PROCAM Study. Prospective Cardiovascular Muenster Study.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the incidence of stroke and the magnitude of classic stroke risk factors in an occupational cohort of white-collar and blue-collar workers. METHODS: We studied a prospective cohort of 12 866 male employees, aged 30 to 65 years, in 52 companies in northwestern Germany, with an average follow-up of 7.2 years. Participants were free of self-reported stroke, transient ischemic attack, and myocardial infarction at baseline. Physical examination, blood tests, and a face-to-face interview to assess presence of various risk factors were performed at the workplace. Follow-up was done by standardized mailed questionnaire. Main outcome measure was first stroke occurrence. RESULTS: Overall stroke incidence was 42.4 per 100000 person-years, increasing from 10.1 per 100000 person-years in the age category 30 to 39 years to 33.6, 80.6, and 159.2 per 100000 person-years in the age categories 40 to 49, 50 to 59, and 60 years and older, respectively. After adjustment for potential confounders, the relative risks of total stroke associated with systolic blood pressure < or = 120, 121 to 140, and > or = 141 mm Hg were 1.00 (reference), 2.99 (95% confidence interval, 0.85 to 10.49), and 5.56 (1.56 to 19.88). The risks associated with smoking status of never/past, < or = 20 cigarettes per day, and >20 cigarettes per day) were 1.00 (reference), 1.65 (0.62 to 4.42), and 3.56 (1.78 to 7.15), respectively. A history of hypertension at baseline (yes versus no) was independently associated with a relative risk of 2.37 (1.20 to 4.71) for total stroke and a history of diabetes mellitus (yes versus no) with a risk of 2.21 (1.00 to 4.87). A comparison of risk factor levels with a general population study revealed only small differences. CONCLUSIONS: This occupational cohort had a 2-fold lower stroke incidence than that observed in cohorts of the general population. In the absence of a strong healthy-worker effect, moderate differences in behavioral risk factors and a higher treatment rate for hypertension contribute to the explanation of this favorable stroke incidence.

Adolescent↗
PubMed1998

PCR-based strategy for the diagnosis of hereditary neuropathy with liability to pressure palsies and Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are inherited peripheral neuropathies. In most cases these disorders are caused by either the duplication (in CMT1A) or the deletion (in HNPP) of a 1.5-megabase DNA fragment on chromosome 17p11.2, which contains the peripheral myelin protein 22 gene (PMP22). We developed a rapid and simple quantitative PCR assay for the detection of the CMT1A duplication or the HNPP deletion. The assay is based on the quantitative determination of the copy number of a 240-base pair DNA fragment from exon 4 of the PMP22 gene. Quantification was done on an automated fluorescence sequencer. Using this method we analyzed four families with the HNPP phenotype. In these families we identified the deletion in all affected individuals. To test the validity of the method, we compared the quantitative PCR results from 50 DNA samples, including 15 samples from individuals with HNPP, 15 samples from CMT1A patients, and 20 from normal controls, with the results obtained by Southern blot analysis. Concordant results were obtained in 49 of the 50 cases.

Blotting, Southern↗
PubMed1998

The Münster Heart Study (PROCAM). Results of follow-up at 8 years.

The Münster Heart Study (PROCAM) was initiated in 1979 in order to examine cardiovascular risk factors, cardiovascular events including myocardial infarction and stroke, and mortality in people at work. Examination at entry comprised a standardized case history, measurement of blood pressure and anthropometric data, a resting electrocardiogram, and measurement of more than 20 laboratory parameters in a fasting blood sample. The prevalence data in this report are based upon a single examination of 17,437 men aged 40.4 +/- 11.3 years (mean +/- SD) and 8065 women aged 35.7 +/- 12.1 years, which took place between 1979 and 1991. Severe hypercholesterolaemia (> 300 mg.dl-1) was seen in 5% of men and 8% of women aged 45 to 64 years. In men, the prevalence of hypertriglyceridaemia (> 200 mg.dl-1) rose from 5% at age 20 to 20% at age 45 and remained constant thereafter; in women the prevalence of hypertriglyceridaemia increased linearly from 2% at age 20 to 7% at age 60. The LDL/HDL ratio was higher in men than in women at all age groups; in the age group 45 to 64 years, LDL/HDL ratios > 5 were approximately twice as common in men. Lipoprotein(a) levels were distributed in a highly skewed fashion. In men, a slight rise in the geometric mean lipoprotein(a) concentration occurred with age, whereas in women a dramatic increase was seen after age 40. Using multivariate analysis by the multiple logistic function method, total cholesterol, HDL cholesterol, LDL cholesterol and log-transformed triglycerides showed a significant (P < 0.001) age-adjusted correlation with the presence of major coronary events. A risk algorithm has been developed for men aged 40 to 65 years which takes into account the independent risk factors of HDL cholesterol, LDL cholesterol, triglycerides, fibrinogen, age, systolic blood pressure, cigarette smoking, presence of diabetes mellitus and family history of myocardial infarction and angina pectoris. This algorithm can be used in clinical practice to calculate the 8-year risk of an individual suffering a myocardial infarction.

Adult↗
PubMed1998

Lipoproteins and cardiovascular risk--from genetics to CHD prevention.

Increased levels of low density lipoprotein (LDL) cholesterol and triglyceride, and low levels of high density lipoprotein (HDL) cholesterol, are associated with increased risk of coronary heart disease (CHD). Only a minor part of the variation in lipids can be explained by defects in single genes of large effect; the bulk of variation in most cases is due to the interaction of polygenes and environment. This paper describes a strategy for unravelling such complex genetic effects in the population at large. A person's risk of developing CHD is, however, not determined by levels of circulating lipids alone, but by a number of factors which contribute to his or her global risk. Based on the data of the Münster Heart Study (PROCAM), a multiple logistic function using nine independent variables for the prediction of risk has been developed. This function allows an almost 40-fold degree discrimination in risk between persons in the lowest and highest quintiles of the algorithm. Data from the Münster Heart Study and other prospective studies indicates a log-linear relationship between LDL cholesterol and CHD risk. The results of recent large scale intervention trials indicate that this relationship also holds true for LDL levels which are achieved by treatment. This indicates that the benefit achieved by cholesterol lowering is greatest at high baseline LDL cholesterol levels, and that at least for LDL cholesterol levels of > or = 80 mg. dl-1, there is no theoretical threshold below which lowering of LDL cholesterol cannot be expected to reduce CHD risk. However, at low LDL cholesterol levels the benefits of treatment may be outweighed by side-effects and by practical cost-benefit considerations. These issues are also discussed in detail in the present report.

Cholesterol↗
PubMed1998

Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I.

Plasmas of patients with Tangier disease (TD) lack lipid-rich alpha-HDL which, in normal plasma, constitutes the majority of high density lipoprotein (HDL). Residual amounts of apolipoprotein (apo)A-I in TD plasma occur as lipid-poor or even lipid-free prebeta-HDL. By contrast to normal plasma, TD plasma does not convert prebeta-HDL into alpha-HDL. Moreover, fibroblasts of TD patients were found to be defective in secreting cholesterol or phospholipids in the presence of lipid-free apoA-I. We have therefore hypothesized that both defective conversion of prebeta-HDL into alpha-HDL and defective lipid efflux from TD cells onto lipid-free apoA-I result from a disturbance in phospholipid transfer occurring in both cellular and extracellular compartments. To test this hypothesis we established an assay that measures the activity of plasma, cells, and cell culture media to transfer radiolabeled phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) from vesicles onto apoA-I, apoA-II, albumin, or reconstituted HDL. Plasmas, HDL, and lipoprotein-depleted plasma of normolipidemic probands as well as cell homogenates and culture media of normal fibroblasts were active at 37 degrees C but not at 4 degrees C in transferring radiolabeled PC, PI, and PE dose- and time-dependently onto either lipid-free apoA-I or reconstituted HDL. Transfer of glycerophospholipids onto apoA-II was much lower than onto apoA-I; transfer onto albumin was close to background. Compared to ten normolipidemic plasmas and four apoA-I-deficient plasmas, plasmas of six TD patients were significantly reduced by 40-50% in their glycerophospholipid transfer activities. Compared to eight normal fibroblast cell lines, homogenates and culture media of four TD fibroblast cell lines were reduced by 40-50% and 30-35%, respectively, in their activity to transfer PC, PI, or PE onto apoA-I. Our data suggest that in TD the same mechanism underlies both defective conversion of prebeta-HDL into alpha-HDL and impaired efflux of cellular lipids, namely a defective phospholipid transfer.

Adult↗
PubMed1998

Failure to confirm ferritin and caeruloplasmin as risk factors for the angiographic extent of coronary arteriosclerosis.

BACKGROUND: It has been suggested that iron overload, as assessed by increased serum ferritin concentration, may be a risk factor for coronary artery disease (CAD). Recent studies have reported conflicting data on the role of ferritin and other parameters of oxidative metabolism in CAD. OBJECTIVE: The aim of this study was to assess the relation between the extent of CAD and parameters of oxidation. METHODS: We studied 275 patients (208 men aged 55.1 +/- 9.6 years and 67 women aged 54.6 +/- 10.0 years) who underwent coronary angiography or percutaneous transluminal coronary angioplasty for the first time. The parameters assessed were: iron, ferritin, transferrin, copper, caeruloplasmin and lipid. Cinefilms were assessed by the use of three scores: (1) Vessel score: 0-3 points; 1 point for each of the three main coronary arteries with a stenosis >70%. (2) Stenosis score: 0-32 points; the coronary artery tree was divided into eight segments that were scored 1-4 points per segment with respect to the maximal degree of stenosis. (3) Extent score: 0-100 points; extent of diffuse coronary lesions in each segment in relation to the length of the vessel. Multiple regression analyses were used to evaluate the results. RESULTS: Total cholesterol and low-density lipoprotein cholesterol (P < 0.001) in women, low-density lipoprotein cholesterol (P < 0.05) in men, and patient age showed a significant correlation with all three scores, but none of the parameters of oxidative metabolism (iron, transferrin, ferritin, copper, caeruloplasmin) correlated significantly with any of the three scores. CONCLUSION: This study demonstrated a correlation between lipoproteins and the angiographic extent of CAD, but did not confirm a role for serum ferritin and other oxidative parameters as risk factors for the extent of CAD.

Adult↗
PubMed1998

Elecsys TSH, FT4, T4, T-uptake, FT3 and T3. Clinical results of a multicentre study.

6 assays for the assessment of thyroid function (TSH, FT4, T4, T-uptake, FT3 and T3) were targets of the International Multicenter Study on the random access analyzer Elecsys 2010. The aim of the study was to characterize the clinical performance of the assay in method comparison and reference range studies. The assays under evaluation were compared to a broad variety of radio isotopic and non-radio isotopic assays. They are suitable for serum and plasma samples. In case of TSH the study include 2nd and 3rd generation TSH procedures. In general, good to excellent correlations were found between the Elecsys and the respective routine methods. Systematic deviations were extraordinary low in case of TSH, FT4 and T4. Regarding the analysis of T3 and FT3 some systematic deviations in terms of standardization have been observed. Results of Elecsys T4 and Elecsys FT4 were independent of the serum total protein or serum albumin concentrations. In T3 and FT3 Elecsys the results of samples from NTI (non-thyroidal-illness) patients were decreased, reflecting the physiological situation in these patients. Studies using samples from healthy euthyroid as well as untreated hypo- and hyperthyroid individuals enabled us to assess the assays reference ranges.

Humans↗
PubMed1998

Elecsys CEA, PSA and AFP. Clinical results of a multicentre evaluation.

Three tumormarker assays, Elecsys CEA, PSA and AFP, have been evaluated in an international multicentre study to characterize their clinical performance and to verify the comparability with the corresponding tests of the Enzymun-Test product line and other methods. For each of the markers results were obtained from four laboratories. On the basis of 314 and 199 specimens respectively, (preliminary) reference ranges could be established for CEA and PSA. For the prostate marker, the age dependence of the antigen level could be clearly confirmed. Mean concentrations range between 0.51 ng/ml (< 40 years) and 3.57 ng/ml (> 70 years). Referring to CEA, 95th percentiles of 4.31 ng/ml and 2.69 ng/ml were elaborated for smokers and nonsmokers. In general, good to excellent correlations (r > 0.98) were found between the Elecsys and Enzymun-Tests. Regarding the systematic comparability of both systems, most of the slopes derived from the individual method comparison studies are within the +/- 10% range of the respective standardization results. The specific distribution pattern of the individual tumormarker values elaborated with sample material of known clinical background, reflects the well established categorization of different benign and malignant diseases according to their characteristic marker levels. Of utmost importance, however, is the excellent comparability of the Elecsys assays with the corresponding Enzymun-Tests and the FDA approved AIA 1200 tests from TOSOH in follow-up studies. Almost superimposable concentration curves guarantee that identical diagnostic information is derived from all three methods. Especially for PSA, a series of measurements on sera of prostatectomized patients proved the usability and clinical value of the test also for this particular indication. For either one of the Elecsys tests, the feasibility of using plasma as sample material was verified.

Adult↗
PubMed1998

Results of the multicentre evaluation of an electrochemiluminescence immunoassay for HCG on Elecsys 2010.

This study evaluated the performance of the HCG STAT Elecsys assay in 8 European laboratories using the Elecsys 2010 system. Analytical sensitivity was < 0.5 mlU/mL. The analysis of concentration series prepared by mixing serum pools with high and low HCG concentrations proved linearity up to 10.000 mIU/mL. A high-dose hook effect was not seen up to HCG concentrations of 430.000 mIU/mL. The medians of the within-run CVs (n = 21, 3 series) were 3.0% (2.1-5.8% CV; 10.4-14.4 mIU/mL), 2.4% (1.7-6.1% CV; 35.6-88.6 mIU/mL) and 2.3% (1.7-6.1% CV; 282.3-643.8 mIU/mL). The medians of the between-day imprecisions (n = 10-21) were 7.0% CV (5.2-12.0% CV; 4.0-14.0 mIU/mL), 5.5% CV (3.1-7.2% CV; 35.4-92.7% mIU/mL) and 4.1% CV (2.8-5.1% CV; 270.8-658.0 mIU/mL). The median recovery of two external quality control samples with assigned values of 9.39 and 10.40 mIU/mL) were 101.2 and 104.3% (ranges: 94.8-116.1%, 98.6-117.8%, n = 10). The assay was compared with five non-isotopic automated routine immunoassay systems (x). Slopes ranged from 0.87 to 1.15 and intercepts from-0.53 to 12.50 mIU/mL. The coefficients of correlation were with one exception (0.898) > or = 0.960. The distribution of HCG in samples from non-pregnant women and healthy men was very similar to that observed with other automated routine methods. The HCG Elecsys assay is very specific for the intact holo-hormone. Nicked HCG dimer, nicked and non-nicked beta-subunits are weakly recognised or not detected. Hemoglobin, bilirubin and lipemia (tested up to: Hb, 3.7 g/L; bilirubin, 500 mumol/L; triglyceride, 37.6 mmol/L) did not interfere the assay. The HCG Elecsys assay is well suited for the early and fast diagnosis of normal pregnancy and the detection of tubal pregnancy.

Adult↗
PubMed1998

Identification of oxidized low-density lipoprotein in human serum by NMR spectroscopy.

1. In this study we compared the 500 MHz 1H-NMRs from native and oxidized low-density lipoproteins. 2. The measurements revealed a characteristic pattern of three resonances in spectra from oxidized, but not from native low-density lipoprotein at 1.17 p.p.m., 1.18 p.p.m. and 1.20 p.p.m. (relative to 3-trimethylsilyl-[2,2,3, 3-2H4]-propionate).3.A quantitative comparison between these resonances in sera from patients with coronary heart disease and healthy control subjects revealed that the intensity was significantly higher in patients with coronary heart disease (1.17 p.p.m.: 0.026+/-0.014 versus 0.015+/-0.019; 1.18 p.p.m.: 0.032+/-0.011 versus 0.017+/-0.021; 1.20 p.p.m.: 0.030+/-0.066 versus 0.010+/-0.005; P<0.05 compared with healthy control subjects for each resonance).4.Fractionation of sera from patients with coronary heart disease revealed that the resonances equal to those obtained from experimentally oxidized low-density lipoprotein are indeed caused by the low-density lipoprotein fraction of the sera.5. When the NMRs from sera were calibrated with oxidized low-density lipoprotein prepared by Cu2+ oxidation, a concentration of 66.5+/-28.6 microgram/ml and 36.3+/-23.7 microgram/ml (P<0.05) was estimated in patients with coronary heart disease and healthy subjects respectively. Elevated levels of oxidized low-density lipoprotein also occurred in those patients with normal serum concentrations of total low-density lipoprotein.6. The study shows a simple method to measure oxidized low-density lipoprotein in human serum and may gain interest to assess the cardiovascular risk factor profiles more completely.

Case-Control Studies↗
PubMed1998

The emergence of triglycerides as a significant independent risk factor in coronary artery disease.

The Prospective Cardiovascular Münster (PROCAM) study involved 4849 middle-aged men who were followed up for 8 years to record the incidence of coronary heart disease (CHD) events according to the risk factors present at study entry. The study showed that fasting levels of triglycerides were an independent risk factor for CHD events, irrespective of serum levels of high density lipoprotein cholesterol (HDL-C) or low density lipoprotein cholesterol (LDL-C). Other independent predictors of CHD included serum levels of LDL-C and HDL-C, age, systolic blood pressure, cigarette smoking, diabetes mellitus, a family history of myocardial infarction and angina pectoris, but did not include total serum cholesterol levels. Individuals with an LDL-C/HDL-C ratio > 5 had a 19.2% chance of experiencing a CHD event in the next 8 years. Furthermore, if an LDL-C/HDL-C ratio > 5 was combined with hypertriglyceridaemia (> or = 2.3 mmol. l-1), the risk of CHD increased to 26.9%. The association between hypertriglyceridaemia and CHD events may be related to the presence of atherogenic, triglyceride-rich particles in plasma, such as LDL and very low density lipoproteins. High triglyceride levels may also predispose to thrombosis. Individuals with potentially atherogenic lipid profiles should be managed initially through the introduction of lifestyle changes. However, if these fail to achieve recommended target values, lipid-lowering therapy should be considered.

Anticholesteremic Agents↗
PubMed1998

Diagnosis and management of new cardiovascular risk factors.

Independent risk factors for coronary heart disease (CHD) can best be identified by means of long-term prospective epidemiological studies. These factors should not be viewed in isolation, but as part of a complex governing a person's global risk of CHD. In the Münster Heart Study (PROCAM), 8-year follow up of a cohort of middle-aged men has led to the identification of nine variables which independently contribute to CHD risk: age, smoking history, personal history of angina pectoris, family history of myocardial infarction (MI), presence of diabetes mellitus, systolic blood pressure and the levels of low density lipoprotein (LDL) cholesterol, high density lipoprotein cholesterol and triglyceride. An algorithm based on these risk factors may be used to calculate an individual's risk of fatal or non-fatal MI and is available in interactive fashion on the website of the International Task Force for Prevention of Coronary Heart Disease at www.chd-taskforce.com. Treatment goals for LDL cholesterol depend on a person's level of risk: for persons with a small increase in risk 160 mg x dl(-1), for those with a moderate increase in risk 135 mg x dl(-1) and for those at high risk, including those with a history of CHD (secondary prevention) 100 mg x dl(-1). Intervention trials indicate that lowering of LDL cholesterol for 5 years produces much of the benefit predicted from the epidemiological data. The place of newer risk markers such as Lp(a), homocysteine, and parameters of clotting and inflammation in risk prediction and management remains to be determined.

Cohort Studies↗
PubMed1997

Phosphatidylcholine-specific phospholipase C regulates thapsigargin-induced calcium influx in human lymphocytes.

The involvement of phosphatidylcholine-specific phospholipase C (PC-PLC) and D (PC-PLD) in the regulation of the thapsigargin-induced Ca2+ increase was investigated. Pretreatment of human lymphocytes with the PC-PLC inhibitors D609 or U73122 enhanced the thapsigargin-induced Ca2+ influx. By contrast, no effect was observed in the presence of phospholipase D inhibitor butanol. Addition of exogenous PC-PLC but not PC-PLD to lymphocytes prestimulated with thapsigargin led to a decrease of intracellular Ca2+. In addition, thapsigargin was shown to release diacylglycerol (DAG) from cellular phosphatidylcholine pools. The thapsigargin-induced DAG formation was inhibited by U73122 and D609 but not by butanol. Moreover, no formation of the PC-PLD activity marker phosphatidylbutanol was detected. Thapsigargin-induced DAG formation was dependent on the Ca2+ entry, as it was abolished in the absence of extracellular Ca2+ or in the presence of Ni2+. Further investigations demonstrated that the inhibition of the cellular DAG target, protein kinase C (PKC), enhanced thapsigargin-induced Ca2+ increase, whereas direct PKC activation had an inhibitory effect. Taken together, our results reveal the involvement of PC-PLC in the regulation of the thapsigargin-induced Ca2+ increase and point to the existence of a physiologic feedback mechanism activated by Ca2+ influx and acting via consecutive activation of PC-PLC and PKC to limit the rise of intracellular Ca2+.

Bridged-Ring Compounds↗