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1.
Ayhan S Tugay C Norton S Araneo B Siemionow M 《Plastic and reconstructive surgery》2003,111(7):2286-2294
Adhesion molecules contribute to ischemia-reperfusion injury by increasing the endothelial adhesion and extravasation of leukocytes. Scientific evidence suggests that presurgical treatment with dehydroepiandrosterone may protect the microvasculature against this damage, but the exact mechanism is not known. The purpose of this study was to investigate the effects of presurgical dehydroepiandrosterone treatment on microcirculatory hemodynamic parameters and the expression of adhesion molecules in a rat cremaster muscle flap model. Twenty male rats were randomly assigned to three experimental groups. In group I (n = 5), the muscle flaps did not receive presurgical treatment. In group II (n = 6), propylene glycol (30 mg/kg), the vehicle for dehydroepiandrosterone, was injected intravenously before ischemia was induced. In group III (n = 9), dehydroepiandrosterone (30 mg/kg) was injected intravenously before ischemia was induced. All flaps were subjected to 6 hours of ischemia and 90 minutes of reperfusion. Microcirculatory variables (functional capillary density, red blood cell velocity in the main flap arteriole, and numbers of rolling, sticking, and transmigrating leukocytes), blood levels of three adhesion molecules (L-selectin, Mac-1 integrin, and CD44), and the numbers of leukocytes expressing those molecules were analyzed. Analysis of the microcirculatory parameters revealed that dehydroepiandrosterone treatment before ischemia had significant preservative effects on the red blood cell velocity and functional capillary density 30 and 90 minutes after reperfusion, compared with the control and vehicle-treated groups. Leukocyte-endothelial cell interactions were also affected by dehydroepiandrosterone treatment, as reflected by significant decreases in the numbers of sticking and transmigrating leukocytes 30 and 90 minutes after reperfusion. In dehydroepiandrosterone-treated animals, leukocytes exhibited lower levels of expression of adhesion molecules after the onset of ischemia, compared with the control groups. In this study, intravenous dehydroepiandrosterone administration reduced the activation of leukocytes and improved red blood cell velocity and capillary perfusion in the muscle flap microcirculation during ischemia-reperfusion injury. This protective effect was most likely the result of delayed expression of Mac-1 integrin, L-selectin, and CD44 molecules on leukocytes. 相似文献
2.
Cardiac alpha-myosin (MYH6) is the predominant sarcomeric disease gene for familial atrial septal defects 总被引:1,自引:0,他引:1
3.
Cigremis Y Parlakpinar H Polat A Colak C Ozturk F Sahna E Ermis N Acet A 《Molecular and cellular biochemistry》2006,285(1-2):149-154
Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic that has cardiotoxicity as a major side effect. One mechanism of this toxicity is believed to involve the reactive oxygen radical species (ROS); these agents likely account for the pathophysiology of DOX-induced cardiomyopathy. Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against ROS formation. We investigated the effects of AG on DOX-induced changes in thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content. The rats were divided into four groups:1) Control; 2) DOX group; injected intraperitoneally (i.p.) with DOX 20 mg/kg in a single dose 3) AG-treated group; injected i.p. in single dose of 20 mg/kg DOX plus 100 mg/kg AG 1 h before the DOX for 3 days, 4) AG group; injected i.p. with AG 100 mg/kg for 3 days. DOX administration to control rats increased TBARS and decreased GSH levels. AG administration before DOX injection caused significant decrease in TBARS and increase in GSH levels in the heart tissue when compared with DOX only. Morphological changes, including severe myocardial fibrosis and inflammatory cell infiltration were clearly observed in the DOX-treated heart. AG reversed the DOX-induced heart damage. Therefore AG could protect the heart tissue against free radical injury. The application of AG during cancer chemotherapy may attenuate tissue damage and improve the therapeutic index of DOX. 相似文献
4.
Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperature and cooling agents,
such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of environmental cold stress such
as cold allodynia in dorsal root ganglion (DRG) neuron; however, the underlying mechanisms of action are unclear. We tested
the effects of physiological heat (37°C), anthralic acid (ACA and 0.025 mM), 2-aminoethyl diphenylborinate (2-APB and 0.05)
on noxious cold (10°C) and menthol (0.1 mM)-induced TRPM8 cation channel currents in the DRG neurons of rats. DRG neurons
were freshly isolated from rats. In whole-cell patch clamp experiments, TRPM8 currents were consistently induced by noxious
cold or menthol. TRPM8 channels current densities of the neurons were higher in cold and menthol groups than in control. When
the physiological heat is introduced by chamber TRPM8 channel currents were inhibited by the heat. Noxious cold-induced Ca2+ gates were blocked by the ACA although menthol-induced TRPM8 currents were not blocked by ACA and 2-APB. In conclusion, the
results suggested that activation of TRPM8 either by menthol or nociceptive cold can activate TRPM8 channels although we observed
the protective role of heat, ACA and 2-APB through a TRPM8 channel in nociceptive cold-activated DRG neurons. Since cold allodynia
is a common feature of neuropathic pain and diseases of sensory neuron, our findings are relevant to the etiology of neuropathology
in DRG neurons. 相似文献
5.
Guo W Schafer S Greaser ML Radke MH Liss M Govindarajan T Maatz H Schulz H Li S Parrish AM Dauksaite V Vakeel P Klaassen S Gerull B Thierfelder L Regitz-Zagrosek V Hacker TA Saupe KW Dec GW Ellinor PT MacRae CA Spallek B Fischer R Perrot A Özcelik C Saar K Hubner N Gotthardt M 《Nature medicine》2012,18(5):766-773
6.
The molecular geometries, normal mode frequencies, intensities and corresponding infrared assignments of monomeric and dimeric
2,3-dimethylpyridine, 2,4-dimethylpyridine, 3,4-dimethylpyridine, 3,5-dimethylpyridine and monomeric 2,6-dimethylpyridine
in the ground state were investigated at the density functional theory (DFT)-B3LYP level using the 6-311+G(d, p) basis set.
The vibrational frequencies and geometric parameters of C–H stretching and bending in the fundamental region were calculated
and compared to the Fourier transform infrared (FT-IR) data obtained. In the studied monomeric and dimeric dimethyl substituted
pyridine derivatives, the C–H stretching and bending frequency shifts that occur between the dimer and the monomer may be
diagnostic of the magnitude of dimerization energy. As supported by data in the literature, the most stable dimeric form was
obtained for the 3,4-dimethylpyridine molecule.
Figure Molecular model and numbering scheme of the studied dimeric dimethylpyridinederivatives 相似文献
7.
Anna N. Panek Maximilian G. Posch Natalia Alenina Santhosh K. Ghadge Bettina Erdmann Elena Popova Andreas Perrot Christian Geier Rainer Dietz Ingo Morano Michael Bader Cemil ?zcelik 《PloS one》2009,4(8)
Connective tissue growth factor (CTGF) is a secreted protein that is strongly induced in human and experimental heart failure. CTGF is said to be profibrotic; however, the precise function of CTGF is unclear. We generated transgenic mice and rats with cardiomyocyte-specific CTGF overexpression (CTGF-TG). To investigate CTGF as a fibrosis inducer, we performed morphological and gene expression analyses of CTGF-TG mice and rat hearts under basal conditions and after stimulation with angiotensin II (Ang II) or isoproterenol, respectively. Surprisingly, cardiac tissues of both models did not show increased fibrosis or enhanced gene expression of fibrotic markers. In contrast to controls, Ang II treated CTGF-TG mice displayed preserved cardiac function. However, CTGF-TG mice developed age-dependent cardiac dysfunction at the age of 7 months. CTGF related heart failure was associated with Akt and JNK activation, but not with the induction of natriuretic peptides. Furthermore, cardiomyocytes from CTGF-TG mice showed unaffected cellular contractility and an increased Ca2+ reuptake from sarcoplasmatic reticulum. In an ischemia/reperfusion model CTGF-TG hearts did not differ from controls.Our data suggest that CTGF itself does not induce cardiac fibrosis. Moreover, it is involved in hypertrophy induction and cellular remodeling depending on the cardiac stress stimulus. Our new transgenic animals are valuable models for reconsideration of CTGF''s profibrotic function in the heart. 相似文献
8.
A myomesin mutation associated with hypertrophic cardiomyopathy deteriorates dimerisation properties
Siegert R Perrot A Keller S Behlke J Michalewska-Włudarczyk A Wycisk A Tendera M Morano I Ozcelik C 《Biochemical and biophysical research communications》2011,(3):473-479
Myomesin plays an important structural and functional role in the M-band of striated muscles. The C-terminal domain 13 of myomesin dimerises and forms antiparallel strands which cross-link neighboring Myosin filaments and titin in the M-line of the sarcomeres. These interactions stabilise the contractile apparatus during striated muscle contraction. Since myomesin is an important component of the M-band we screened the myomesin gene for genetic variants in patients with hypertrophic cardiomyopathy (HCM).We identified the missense mutation V1490I in domain 12 of myomesin in a family with inherited HCM. Analytical ultracentrifugation experiments, circular dichroism spectra, and surface plasmon resonance spectroscopy of myomesin fragments were carried out to investigate the effects of the mutation V1490I on structure and function of myomesin domains 11–13 and 12–13. Both the wild type and mutated myomesin domains My11–13 revealed similar secondary structures and formed stable dimers. Mutated myomesin domains My11–13 and My12–13 dimers revealed a reduced thermal stability and a significantly decreased dimerisation affinity, showing disturbed functional properties of V1490I mutated myomesin. However, monomeric myomesin domains My11–12, i.e. without dimerisation domain 13 showed no difference in thermal stability between wild type and V1490I mutated myomesin.In conclusion, the V1490I mutation associated with HCM lead to myomesin proteins with abnormal functional properties which affect dimerisation properties of myomesin domain 13. These effects may contribute to the pathogenesis of HCM. 相似文献
9.
Glutathione (GSH) is the most abundant thiol antioxidant in mammalian cells and maintains thiol redox in the cells. GSH depletion
has been implicated in the neurobiology of sensory neurons. Because the mechanisms that lead to melastatin-like transient
receptor potential 2 (TRPM2) channel activation/inhibition in response to glutathione depletion and 2-aminoethyldiphenyl borinate
(2-APB) administration are not understood, we tested the effects of 2-APB and GSH on oxidative stress and buthionine sulfoximine
(BSO)-induced TRPM2 cation channel currents in dorsal root ganglion (DRG) neurons of rats. DRG neurons were freshly isolated
from rats and the neurons were incubated for 24 h with BSO. In whole-cell patch clamp experiments, TRPM2 currents in the rat
were consistently induced by H2O2 or BSO. TRPM2 channels current densities and cytosolic free Ca2+ content of the neurons were higher in BSO and H2O2 groups than in control. However, the current densities and cytosolic Ca2+ release were also higher in the BSO + H2O2 group than in the H2O2 alone. When intracellular GSH is introduced by pipette TRPM2 channel currents were not activated by BSO, H2O2 or rotenone. BSO and H2O2-induced Ca2+ gates were blocked by the 2-APB. Glutathione peroxidase activity, lipid peroxidation and GSH levels in the DRG neurons were
also modulated by GSH and 2-APB inhibition. In conclusion, we observed the protective role of 2-APB and GSH on Ca2+ influx through a TRPM2 channel in intracellular GSH depleted DRG neurons. Since cytosolic glutathione depletion is a common
feature of neuropathic pain and diseases of sensory neuron, our findings are relevant to the etiology of neuropathology in
DRG neurons. 相似文献
10.
Gamze Guney Eskiler Asuman Deveci Ozkan Ayten Haciefendi Cemil Bilir 《Translational oncology》2022,15(1)
The therapeutic effects of abemaciclib (ABE), an inhibitor of cyclin- dependent kinases (CDK) 4/6, on the proliferation of two types of prostate cancer (PC) cells were revealed. In this study, in vitro cytotoxic and apoptotic effects of ABE on metastatic castration-resistant prostate cancer (mCRPC) androgen receptor (AR) negative PC-3 and AR mutant LNCaP PC cells were analyzed with WST-1, Annexin V, cell cycle, reactive oxygen species (ROS), mitochondrial membrane potential, RT-PCR, western blot, and apoptosis protein array. ABE considerably inhibited the growth of PC cells in a dose-dependent manner (p<0.01) and caused significant apoptotic cell death through the suppression of CDK4/6-Cyclin D complex, ROS generation and depolarization of mitochondria membrane potential. However, PC-3 cells were more sensitive to ABE than LNCaP cells. Furthermore, the expression levels of several pro-apoptotic and cell cycle regulatory proteins were upregulated by ABE in especially PC-3 cells with the downregulation of apoptotic inhibitor proteins. Our results suggest that ABE inhibits PC cell growth and promotes apoptosis and thus ABE treatment may be a promising treatment strategy in especially mCRPC. Further preclinical and clinical studies should be performed to clarify the clinical use of ABE for the treatment of PC. 相似文献