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Biomedical subjects

H Sauer

Publications and source records attributed to H Sauer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Inhibition of geranylgeranylation reduces angiotensin II-mediated free radical production in vascular smooth muscle cells: involvement of angiotensin AT1 receptor expression and Rac1 GTPase.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may exert pleiotropic effects on vascular cells independent of lowering plasma cholesterol. To elucidate the molecular mechanisms involved in these effects, we investigated the impact of statins on production of reactive oxygen species (ROS) in rat aortic vascular smooth muscle cells (VSMC). Exposure of VSMC to angiotensin II caused production of ROS via angiotensin AT1 receptor activation. Pretreatment with atorvastatin inhibited angiotensin II-induced ROS production. Atorvastatin decreased AT1 receptor mRNA levels in a time- and concentration-dependent manner and consistently reduced AT1 receptor density. L-Mevalonate but not hydroxy-cholesterol reversed the inhibitory effect of atorvastatin on AT1 receptor transcript levels. Inhibition of geranylgeranyl-transferase but not of farnesyl-transferase mimicked the effect of atorvastatin on AT1 receptor gene expression. Atorvastatin did not decrease AT1 receptor gene transcription but did reduce the half-life of the AT1 receptor mRNA. AT1 receptor activation by angiotensin II increased the expression of the GTPase rac1, enhanced rac1 GTP-binding activity, and increased the geranylgeranyl-dependent translocation of rac1 to the cell membrane. In contrast, statins inhibited rac1 activity and membrane translocation. Consequently, specific inhibition of rac1 with Clostridium sordellii lethal toxin blocked angiotensin II-induced production of free radicals. Finally, treatment of rats with atorvastatin caused down-regulation of aortic AT1 receptor mRNA expression and reduced aortic superoxide production in vivo. Cholesterol-independent down-regulation of AT1 receptor gene expression and inhibition of rac1, leading to decreased ROS production, demonstrates a novel regulatory mechanism of statins that may contribute to the beneficial effects of these drugs beyond lowering of plasma cholesterol.

Angiotensin II↗
PubMed2001

Characteristics of calcium sparks in cardiomyocytes derived from embryonic stem cells.

In embryonic stem (ES) cell-derived cardiomyocytes, spontaneous Ca(2+) sparks representing Ca(2+) release through ryanodine receptor (RyR) channels were characterized and correlated to the expression of RyRs as well as the Ca(2+) load of the sarcoplasmic reticulum (SR). In very early developmental stage (VEDS) cardiac precursor cells, global intracellular Ca(2+) concentration ([Ca(2+)](i)) fluctuations occurred, whereas Ca(2+) sparks and contractions were absent. In early developmental stages (EDS), contractions as well as Ca(2+) sparks were obvious. During the further differentiation to late developmental stage (LDS) cardiomyocytes, a marked increase in the frequency of global [Ca(2+)](i) transients, the amplitude and the frequency of Ca(2+) sparks, as well as the expression of RyRs and the volume of RyR-positive SR, was observed. Furthermore, the caffeine-releasable SR Ca(2+) load was elevated in LDS compared with EDS cardiomyocytes. A high-Ca(2+) solution raised spark frequency as well as amplitude in EDS cardiomyocytes to the levels of LDS cardiomyocytes. The characteristics of Ca(2+) sparks occurring in cardiomyocytes differentiated from ES cells may be governed by the Ca(2+) load of the SR and/or the density of RyRs.

Animals↗
PubMed2001

Reactive oxygen species as intracellular messengers during cell growth and differentiation.

Reactive oxygen species (ROS) are generated following ligand-receptor interactions and function as specific second messengers in signaling cascades involved in cell proliferation and differentiation. Although ROS are generated intracellularly by several sources, including mitochondria, the primary sources of ROS involved in receptor-mediated signaling cascades are plasma membrane oxidases, preferentially NADPH oxidases, with a rapid kinetics of activation and inactivation. This allows a tight up- and downregulation of intracellular ROS levels within the short time required for the transduction of signals from the plasma membrane to the cell nucleus. The mode of action of ROS may involve direct interaction with specific receptors, and/or redox-activation of members of signaling pathways such as protein kinases, protein phosphatases, and transcription factors. Furthermore, ROS act in concert with intracellular Ca(2+) in signaling pathways which regulate the balance of cell proliferation versus cell cycle arrest and cell death. The delicate intracellular interplay between oxidizing and reducing equivalents allows ROS to function as second messengers in the control of cell proliferation and differentiation.

Animals↗
PubMed2001

[Quantitative measurement of induced skin reddening using optical reflection spectroscopy--methodology and clinical application].

Optical reflection spectroscopy is a simple and quick method for the quantification of colour intensity, and is thus suitable for the determination of changes in skin reddening (erythema) due to local vasodilatation. To quantify the time course of this erythema, the oxyhaemoglobin absorption double peak with maxima at 542 and 577 nm is an appropriate parameter. A compact handheld optical spectrometer makes the technique applicable to clinical use, an example being the niacin patch test described herein. This noninvasive test provides information about the cell membrane metabolism via the skin flush induced by niacin (vitamin B3) and mediated by prostaglandin. The aim of this study was to adapt optical reflection spectroscopy to the requirements of the clinical niacin patch test. To that end, we investigated 60 healthy volunteers. Analysis of the spectroscopic data with regard to physiological covariables of niacin sensitivity revealed faster and more intense erythema in females--a gender effect that to our knowledge has not previously been reported. In the light of these results, the findings of other researchers based on semi-quantitative test methods should be reassessed, with consideration given to the gender effect.

Adolescent↗
PubMed2001

Measurement of apoptosis in long-term cultures of human ovarian tissue.

At present, the long-term culture of ovarian tissue is problematic. The aim of this study was to measure apoptosis in long-term cultures of human ovarian tissue. Biopsies of human ovaries were cultured for 6 weeks. Samples were taken weekly for histological investigation. The apoptotic cells were marked with anti-caspase 3. Simultaneous to this experiment, other tissue samples were preincubated for 3 h with 1 micromol staurosporine l(-1), an inducer of apoptosis, and apoptosis was compared among samples. Furthermore, the proportion of lethal cells was determined weekly. After 6 weeks, 99% of the tissue samples showed an intact structure. They expanded in all directions on the floor of the multi-wells to form a monolayer. Apoptotic cells could be marked only sporadically (16.3 +/- 5.9 fluorescence (counts per 3600 microm(2))) after 6 weeks. After preincubation with staurosporine after the same period of culture, the proportion of apoptotic cells was significantly increased compared with that in untreated control samples (66.8 +/- 14.5 versus 16.3 +/- 5.9%, respectively; P < 0.05). Under the same experimental conditions, the proportion of lethal cells was 3.6 +/- 0.9, 3.9 +/- 2.1 and 5.2 +/- 1.5% for weeks 1, 3 and 6, respectively. After preincubation with 1 micromol staurosporine l(-1), the proportion of pyknotic cells after 6 weeks of culture was significantly higher (37.2 +/- 4.4%) than that in control samples (3.95 +/- 2.05%; P < 0.05). No significant increase in apoptosis in cultured human ovarian tissue after 6 weeks was observed compared with control tissues on day 1. These results indicate that under optimal culture conditions it is possible to cultivate human ovarian tissue long term. The influence of long-term culture on hormone synthesis and follicle maturity will be investigated further.

Adult↗
PubMed2001

Plague and other human infections caused by Yersinia species.

With an estimated 100 million victims, pandemically and epidemically occurring plague has been looked upon as a classical scourge of mankind during the last two millenia. Without treatment at least 50% of the affected individuals die from infection with Yersinia pestis, a bacterium belonging to the family of Enterobacteriaceae. The disease takes a fulminant course. After an incubation period of 2-6 days, bubonic plague primarily attacks one group of lymph nodes. The onset of pulmonic plague, transmitted by droplet infection, takes place within several hours and causes bronchopneumonia. Early recognition facilitates a promising antibiotic therapy with tetracycline, streptomycin or chloramphenicol. Human beings acquire the bacteria through bites of fleas from domestic rats in densely populated cities of countries with low hygienic standards, or sporadically in the open country from infected wild rodents. Laboratory procedure includes microscopy supplemented by immunofluorescence and cultivation of the bacterium from clinical material. Direct serology and PCR result in a fast detection of specific antigens or nucleotide sequences. Determination of serum antibodies is principally used for epidemiological investigation. Today, physicians in the civilized western world lack experience for the recognition of plague, and analytical techniques for diagnosis are only available in some specialized laboratories. Yersiniosis becomes primarily manifest as gastroenteritis caused by Yersinia enterocolitica or as pseudoappendicitis caused by Yersinia pseudotuberculosis and requires antibiotics only in severe septic cases. Different extraintestinal symptoms may be observed in dependence on the patient's HLA type and gender. The ubiquitous germ is mainly transmitted by the fecal-oral route via infected domestic or farm animals and contaminated food. The relevant virulence factors are encoded on a 70 kB plasmid common to all Yersinia species and strains that are human pathogens. The most important tools for laboratory diagnosis are culture from suitable body fluids and serological detection of specific antibodies. The infection rate among healthy individuals in Europe in terms of percentage of elevated IgA or IgG titers has been quoted to be 3-40% in different investigations but does not significantly correlate to direct bacteriological detection.

Animals↗
PubMed2000

Supporting evidence for the model of cognitive dysmetria in schizophrenia--a structural magnetic resonance imaging study using deformation-based morphometry.

The aim of the study was to investigate whether there is any structural evidence for the model of 'cognitive dysmetria' in schizophrenia if an automatic whole-brain analysis method is used. High-resolution magnetic resonance scans were obtained for 75 schizophrenic patients and 75 controls. These data were analysed using the recently developed deformation-based morphometry allowing the assessment of volumetric differences without a priori definition of regions of interest. When compared with controls, we found reduced volumes in patients with schizophrenia in the frontal lobe (gyrus frontalis superior, medius and medialis), the temporal lobe (gyrus temporalis superior and inferior), the thalamus, the left cerebellar hemisphere and the right cerebellar vermis. There was an increase in volume in the right putamen. To date, this is the first structural magnetic resonance imaging study to demonstrate that the three key-elements of the model of cognitive dysmetria--frontal lobe, thalamus, and cerebellum--are reduced in volume in schizophrenic patients. This highlights the importance of this concept for future investigations.

Adult↗
PubMed2000

Differential effects of estrogen and progesterone on AT(1) receptor gene expression in vascular smooth muscle cells.

BACKGROUND: The beneficial vasoprotective effects of a postmenopausal estrogen replacement therapy may be prevented by a concomitant administration of progestins. To investigate the differential effects of estrogens and progesterone, we examined their influence on AT(1) receptor gene expression in vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: 17beta-Estradiol caused downregulation of AT(1) receptor mRNA expression to 46+/-14%, whereas progesterone led to a significant upregulation to 201+/-29%, as assessed by Northern analysis. Western blots revealed that estrogen induced a downregulation and progesterone an upregulation of the AT(1) receptor protein. Estrogen-induced decrease of AT(1) receptor expression was mediated through activation of estrogen receptors. Nuclear run-on assays revealed that 17beta-estradiol did not alter AT(1) receptor mRNA transcription rate, whereas progesterone caused an enhanced AT(1) receptor mRNA transcription rate. 17beta-Estradiol decreased the AT(1) receptor mRNA half-life from 5 to 2 hours, whereas progesterone induced a stabilization of AT(1) receptor mRNA to a half-life of 10 hours. Preincubation of VSMCs with PD98059, SB203580, herbimycin, wortmannin, or N:(omega)-nitro-L-arginine suggested that 17beta-estradiol caused AT(1) receptor downregulation through nitric oxide-dependent pathways. Progesterone caused AT(1) receptor overexpression via PI(3)-kinase activation. Angiotensin II-induced release of reactive oxygen species was inhibited by estrogens. Progesterone itself enhanced the production of reactive oxygen species. CONCLUSIONS: Because AT(1) receptor regulation plays a pivotal role in the pathogenesis of hypertension and atherosclerosis, the differential effects of estrogen and progesterone on the expression of this gene may in part explain the potentially counteracting effects of these reproductive hormones on the incidence of postmenopausal cardiovascular diseases.

Analysis of Variance↗
PubMed2000

Role of reactive oxygen species and phosphatidylinositol 3-kinase in cardiomyocyte differentiation of embryonic stem cells.

Cardiotypic development in embryonic stem cell-derived embryoid bodies may be regulated by reactive oxygen species (ROS). ROS were generated by a NADPH oxidase-like enzyme which was transiently expressed during the time course of embryoid body development. Incubation with either H(2)O(2) or menadione enhanced cardiomyogenesis, whereas the radical scavengers trolox, pyrrolidinedithiocarbamate and N-acetylcysteine exerted inhibitory effects. The phosphatidylinositol 3-kinase (PI-3-kinase) inhibitors LY294002 and wortmannin abolished cardiac commitment and downregulated ROS in embryoid bodies. Coadministration of LY294002 with prooxidants resumed cardiomyocyte differentiation, indicating a role for PI-3-kinase in the regulation of the intracellular redox state.

Androstadienes↗
PubMed2000

Extracorporeal circulation exacerbates microvascular permeability after endotoxemia.

BACKGROUND: Extracorporeal life support without prior inflammatory stimuli results in a modest increase in microvascular permeability. Initiating ECLS after shock, sepsis, or hypoxia results in marked increases in interstitial fluid and total body water. We sought to determine whether an inflammatory stimulus prior to initiating ECLS increases microvascular permeability to protein. METHODS: An anesthetized canine lymphatic fistula model was used to study Starling forces. LPS + ECLS received 1 mg/kg LPS 1 h prior to initiating ECLS, and the group ECLS received saline vehicle. To determine mesenteric microvascular permeability, mesenteric venous pressure was elevated to 32 +/- 1 mm Hg to reach a minimal lymph protein concentration (C(L)). With simultaneous measurement of plasma protein concentration (C(P)), the reflection coefficient, sigma, was calculated using the formula sigma = 1 - C(L)/C(P). Transvascular protein clearance and filtration coefficient (K(f)) were calculated from the measured Starling variables. After a steady state was achieved, normothermic right atrial-to-femoral artery ECLS was initiated and continued for 2 h and then discontinued. Measurements were continued for 30 min after ECLS was discontinued. Measurements were continued for 30 min after ECLS was discontinued. Within-group comparisons were made with ANOVA and Fisher's LSD, and between-group comparisons were made with Student's t tests where appropriate. RESULTS: The reflection coefficient (sigma) decreased significantly from 0.77 +/- 0.02 to 0.53 +/- 0.07 with LPS + ECLS and was lower compared to ECLS alone (0.77 +/- 0.02 to 0.65 +/- 0.03). Transvascular protein clearance increased to a greater extent in LPS + ECLS from 266 +/- 46 to 819 +/- 125 microl/min compared to ECLS alone (284 +/- 49 to 819 +/- 125 microl/min) (P = 0. 06). K(f) increased in both groups after initiation of ECLS, but to a significantly greater extent in LPS + ECLS at 60 min (30.7 +/- 2.2 microl/min/mm Hg/g in ECLS and 50.0 +/- 8.9 microl/min/mm Hg/g in LPS + ECLS). Ileal tissue water increased in both groups, but there were no differences between groups. CONCLUSIONS: Initiation of ECLS after exposure to LPS increases ileal microvascular permeability to protein and water to a greater extent than ECLS alone.

Animals↗
PubMed2000

Reduced phosphodiesters and high-energy phosphates in the frontal lobe of schizophrenic patients: a (31)P chemical shift spectroscopic-imaging study.

BACKGROUND: (31)Phosphorous magnetic resonance spectroscopy has been widely used to evaluate schizophrenic patients in comparison to control subjects, because it allows the investigation of both phospholipid and energy metabolism in vivo; however, the results achieved so far are inconsistent. Chemical shift imaging (CSI) has the advantage that instead of only one or a few preselected voxels the tissue of a whole brain slice can be examined. The aim of the present investigation was to determine whether the results of previous studies of our group, showing that phosphodiesters (PDE) are decreased in the frontal lobe of schizophrenic patients as compared to control subjects, might be confirmed in an independent unmedicated patient sample using the CSI technique. METHODS: A carefully selected new cohort including 11 neuroleptic-free schizophrenic patients and 11 age- and gender-matched healthy control subjects was recruited. CSI was applied and an innovative analysis method for CSI data based on a general linear model was used. RESULTS: PDE, phosphocreatine, and adenosine triphosphate (ATP) were found to be significantly decreased in the frontal lobe of patients with schizophrenia. CONCLUSIONS: Because PDE was decreased in schizophrenic patients, the membrane phospholipid hypothesis of schizophrenia could not be corroborated. Further results indicate decreased ATP production in the frontal lobe of patients with schizophrenia.

Adenosine Triphosphate↗
PubMed2000

Redox regulation of P-glycoprotein-mediated multidrug resistance in multicellular prostate tumor spheroids.

Multicellular prostate tumor spheroids develop intrinsic P-glycoprotein (Pgp)-mediated multidrug resistance with the appearance of quiescent cell areas. We have investigated the effect of intracellular reactive oxygen species (ROS) on Pgp expression in large, quiescent and drug-resistant multicellular spheroids (diameter 250 +/- 50microm). Using the ROS-sensitive fluorescence dye 2;7;-dichlorodihydrofluorescein diacetate (H(2)DCFDA), we demonstrated that these tumor spheroids are characterized by reduced intracellular ROS compared with drug-sensitive small spheroids (diameter 60 +/- 20microm) consisting predominantly of proliferating cells. The prooxidants hydrogen peroxide, menadione and glyceraldehyde raised ROS in large tumor spheroids and significantly down-regulated Pgp within 24 hr. Comparable effects were achieved with the known Pgp-reversing agents sodium orthovanadate, quinidine and cyclosporin A but not with verapamil. Consequently, the retention and toxicity of the anthracycline doxorubicin was increased in tumor spheroids treated with prooxidants. Co-administration of prooxidants and the free radical scavenger ebselen did not alter Pgp levels, indicating that down-regulation of Pgp is mediated via ROS. Down-regulation of Pgp by H(2)O(2) was abolished when either forskolin, 8-Br-cAMP or IBMX, which raise intracellular cAMP levels, was co-administered, indicating that Pgp expression is regulated by protein kinase A (PKA). Furthermore, Pgp was down-regulated by the PKA inhibitors Rp-cAMPs and H89. Since prooxidants stimulated the growth of multicellular spheroids and down-regulated the cyclin-dependent kinase inhibitor p27(kip1), we conclude that ROS-mediated Pgp down-regulation may be paralleled by recruitment of drug-resistant quiescent cells in the depth of the tumor tissue for cell-cycle activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

[Phosphorus 31 magnetic resonance spectroscopy in schizophrenia research. Pathophysiology of cerebral metabolism of high-energy phosphate and membrane phospholipids].

31Phosphorus nuclear magnetic resonance spectroscopy (31P-MRS) has gained much interest in schizophrenia research in the last years, since it allows noninvasive measurement of high energy phosphates and phospholipids of the human brain in vivo. Thus, several studies have reported cerebral metabolic differences between patients and healthy controls as well as on lateralization effects and influences of epidemiological and psychopathological factors. This review gives a survey of the potential of 31P-MRS in schizophrenia research and summarizes and comments on the results of preceding studies. The discussion covers the reduction of phospholipids in patients in the context of the membrane phospholipid hypotheses, the question of an energetic hypometabolism in schizophrenics, and the influence of neuroleptic medication.

Adenosine Triphosphate↗
PubMed2000

Thalidomide inhibits angiogenesis in embryoid bodies by the generation of hydroxyl radicals.

Thalidomide is a teratogen with anti-angiogenic properties and causes stunted limb growth (dysmelia) during human embryogenesis. The molecular mechanisms of thalidomide action in embryopathy are currently unknown. Using the endothelial-specific antigen platelet endothelial cell adhesion molecule-1 and confocal laser scanning microscopy we have demonstrated that thalidomide exerts anti-angiogenic effects on the development of capillary structures in embryoid bodies differentiated from murine embryonic stem cells. Consequently, in thalidomide-treated embryoid bodies the diffusion properties of the tissue were deteriorated. Thalidomide raised reactive oxygen species (ROS), as revealed using 2'7'-dichlorodihydrofluorescein diacetate (H(2)DCF-DA) as an indicator. A comparable ROS generation was achieved with the thalidomide hydrolysis product phthaloyl glutamic acid (PGA), but not with phthalimide (PI), the major component of thalidomide. ROS formation by thalidomide was inhibited by the hydroxyl radical scavengers mannitol and 2-mercaptoethanol. After coadministration of either 2-mercaptoethanol or mannitol with thalidomide the anti-angiogenic effects of thalidomide were abolished and the diffusion properties of the tissue were restored to the control values. In summary, our data suggest that thalidomide exerts its anti-angiogenic properties via the generation of toxic hydroxyl radicals, which impair vasculogenesis and angiogenesis during embryoid body development.

Angiogenesis Inhibitors↗
PubMed2000

Low and infrequent expression of nitric oxide synthase/NADPH-diaphorase in neurons of the human supraoptic nucleus: a histochemical study.

The gas nitric oxide is a messenger in brain signaling. In the hypothalamo-hypophyseal system nitric oxide is involved in the control of the expression and/or release of peptide hormones (corticotropin-releasing hormone, gonadotropin-releasing hormone, vasopressin and oxytocin). Nitric oxide synthase (NOS), the enzyme generating nitric oxide, is abundantly present in the magnocellular nuclei of the rat hypothalamus. Its localization in the human hypothalamus is less well studied. Hence, we investigated the anatomical distribution of neuronal nitric oxide synthase in the human supraoptic nucleus by use of immunohistochemical and enzyme histochemical techniques. The immunohistochemical localization of NOS was studied in 31 matched human hypothalami (13 control cases, eight depressed patients and ten schizophrenics). NADPH-diaphorase studies were carried out on seven additional hypothalami (three normal brains, four schizophrenics). Apparent inter-individual differences exist with regard to the occurrence of the enzyme in supraoptic neurons. In a majority of cases no immunostaining or histochemical reaction for the enzyme was observed. In seven cases (three controls, two schizophrenics, two depressives) a population of nitrergic nerve cells was seen in the dorsomedial part of the nucleus. This group of cells also stained for NADPH-diaphorase. Also, there were a few NOS-immunopositive neurons scattered throughout the nucleus. Additionally, thin NADPH-diaphorase positive fibers were observed to cross the nucleus. Our data show that, unlike the rat, the human supraoptic nucleus contains only a small number of nitrergic neurons. No correlation was found between the expression of the enzyme in supraoptic neurons and the psychiatric status of the patients.

Aged↗
PubMed2000

Negative feedback regulation of reactive oxygen species on AT1 receptor gene expression.

Free radicals as well as the AT1 receptor are involved in the pathogenesis of cardiovascular disease. Both the intracellular mechanisms of AT1 receptor regulation and the effect of free radicals on AT1 receptor expression are currently unknown. This study investigates the role of free radicals in the modulation of AT1 receptor expression and in the angiotensin II-induced AT1 receptor regulation. AT1 receptor mRNA was assessed by Northern blotting and AT1 receptor density by radioligand binding assays, respectively, in vascular smooth muscle cells (VSMC). Free radical release was measured by confocal laser scanning microscopy. AT1 receptor mRNA transcription rate was determined by nuclear run-on assays and AT1 receptor mRNA half-life was measured under transcriptional blockade. Angiotensin II caused a time-dependent decrease of AT1 receptor mRNA expression in rat VSMC in culture (30+/-6% at 4 h with 100 nM angiotensin II). This was followed by a consistent decrease in AT1 receptor density. Angiotensin II caused release of reactive oxygen species in VSMC which was abolished by preincubation with 100 microM diphenylene iodonium (DPI). DPI inhibited partially the down-regulating effect of angiotensin II on the AT1 receptor. Incubation of VSMC with either hydrogen peroxide or xanthine/xanthine oxidase caused a dose-dependent decrease in AT1 receptor mRNA expression which was not mediated by a decreased rate of transcription but rather through destabilization of AT1 receptor mRNA. Experiments which included preincubation of VSMC with various intracellular inhibitors suggested that free radicals caused AT1 receptor downregulation through activation of p38-MAP kinase and intracellular release of calcium. However, angiotensin II-induced AT1 receptor expression was not inhibited by blockade of p38-MAP kinase activation or intracellular calcium release. Free radicals may at least in part mediate angiotensin II-induced AT1 receptor regulation through direct post-transcriptional effects on AT1 receptor mRNA expression which involves intracellular release of calcium and activation of p38-MAP kinase. These findings may help to clarify the intracellular mechanisms involved in AT1 receptor regulation and reveal a novel biological feature for reactive oxygen species.

Animals↗