Different types of contractions in rat colon and their modulation by oxidative stress

2001 ◽  
Vol 280 (4) ◽  
pp. G546-G554 ◽  
Author(s):  
Asensio Gonzalez ◽  
Sushil K. Sarna
Keyword(s):  
Potential Role ◽  
Contractile Response ◽  
Circular Muscle ◽  
Distal Colon ◽  
Proximal Colon ◽  
Rat Colon ◽  
Hla B27 ◽  
Different Types

The aim of this study was to investigate the modulation of in vitro rat colonic circular muscle contractions by dextran sodium sulfate (DSS)-induced inflammation and in spontaneous inflammation in HLA-B27 rats. We also examined the potential role of hydrogen peroxide (H2O2) in modulating excitation-contraction coupling. The muscle strips from the middle colon generated spontaneous phasic contractions and giant contractions (GCs), the proximal colon strips generated primarily phasic contractions, and the distal colon strips were mostly quiescent. The spontaneous phasic contractions and GCs were not affected by inflammation, but the response to ACh was suppressed in DSS-treated rats and in HLA-B27 rats. H2O2production was increased in the muscularis of the inflamed colon. Incubation of colonic muscle strips with H2O2suppressed the spontaneous phasic contractions and concentration and time dependently reduced the response to ACh; in the middle colon, it also increased the frequency of GCs. We conclude that H2O2mimics the suppression of the contractile response to ACh in inflammation. H2O2also selectively suppresses phasic contractions and increases the frequency of GCs, as found previously in inflamed dog and human colons.

Dietary flavonol quercetin induces chloride secretion in rat colon

1998 ◽  
Vol 275 (5) ◽  
pp. G1166-G1172 ◽  
Author(s):  
Rainer Cermak ◽  
Ursula Föllmer ◽  
Siegfried Wolffram
Keyword(s):  
Short Circuit ◽  
Ussing Chamber ◽  
Phosphodiesterase Inhibitor ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Proximal Colon ◽  
Rat Colon ◽  
Quercetin Glycoside

The aim of this study was to investigate the possible effects of the flavonol quercetin, the most abundant dietary flavonoid, on the intestinal mucosa. In vitro experiments were performed with various segments of the rat intestine, using the Ussing chamber technique. Quercetin increased the short-circuit current ( I sc) in the jejunum, ileum, and proximal and distal colon. Additional experiments were performed using preparations of the proximal colon. The maximum effective dose of quercetin was found to be ∼100 μM. The quercetin-induced increase in I sc was inhibited by the Cl− channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoic acid. Adding blockers of the Na+-K+-2Cl−cotransporter to the serosal compartment diminished the increase of I sc due to quercetin. Ion substitution and flux measurements indicated that the effect of quercetin was due to electrogenic Cl− and[Formula: see text] secretion. In contrast to the aglycone, the quercetin glycoside rutin had no effect. The effect of quercetin on I scwas additive to the I sc increase induced by forskolin, but the flavonoid diminished the I sc evoked by carbachol. The phosphodiesterase inhibitor theophylline blocked the effect of quercetin. Genistein, a related isoflavone, did not alter the I sc evoked by quercetin. These findings demonstrate that the dietary flavonol quercetin induces Cl−secretion and most likely [Formula: see text]secretion in rat small and large intestine. The effects are restricted to the flavonol aglycone.

scholarly journals Src family kinase involvement in rat preglomerular microvascular contractile and [Ca2+]iresponses to ANG II

2005 ◽  
Vol 288 (4) ◽  
pp. F658-F664 ◽  
Author(s):  
Qi Che ◽  
Pamela K. Carmines
Keyword(s):  
Potential Role ◽  
Contractile Response ◽  
Ang Ii ◽  
Src Family Kinase ◽  
Kinase Inhibition ◽  
Juxtamedullary Nephron ◽  
Inactive Analog ◽  
Baseline Diameter

Experiments were performed to investigate the potential role of Src family kinase(s) in the rat afferent arteriolar contractile response to ANG II. The in vitro blood-perfused juxtamedullary nephron technique was employed to monitor afferent arteriolar lumen diameter responses to 1–100 nM ANG II before and during Src family kinase inhibition (10 μM PP2). PP2 did not alter baseline diameter but attenuated ANG II-induced contractile responses by 33 ± 6%. An inactive analog of PP2 (PP3) had no effect on ANG II-induced afferent arteriolar contraction. The effect of Src kinase inhibition on ANG II-induced intracellular free Ca2+concentration ([Ca2+]i) responses was probed in fura 2-loaded preglomerular microvascular smooth muscle cells (PVSMCs) obtained from explants and studied after 3–5 days in culture. In untreated PVSMCs, ANG II evoked peak (Δ = 293 ± 66 nM) and plateau (Δ = 23 ± 8 nM) increases in [Ca2+]i. In PVSMCs pretreated with PP2, baseline [Ca2+]iwas unaltered, but both the peak (Δ = 140 ± 22 nM) and plateau (Δ = 3 ± 2 nM) phases of the ANG II response were significantly reduced compared with untreated cells. PP3 did not alter [Ca2+]iresponses to ANG II. Immunoprecipitation and Western blot analysis confirmed that 100 nM ANG II increased phosphorylation of c-Src (at Y416) in PVSMCs. The phosphorylation response was maximal 1 min after ANG II exposure and was prevented by PP2. We conclude that the preglomerular vasoconstriction evoked by ANG II involves rapid c-Src activation with subsequent effects that contribute to the [Ca2+]iresponse to the peptide.

scholarly journals Specificity of the HIV-1 Protease on Substrates Representing the Cleavage Site in the Proximal Zinc-Finger of HIV-1 Nucleocapsid Protein

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1092
Author(s):  
János András Mótyán ◽  
Márió Miczi ◽  
Stephen Oroszlan ◽  
József Tőzsér
Keyword(s):  
Amino Acid ◽  
Zinc Finger ◽  
Cleavage Site ◽  
Potential Role ◽  
Binding Mode ◽  
Interaction Energies ◽  
Vitro Assay ◽  
Hiv 1

To explore the sequence context-dependent nature of the human immunodeficiency virus type 1 (HIV-1) protease’s specificity and to provide a rationale for viral mutagenesis to study the potential role of the nucleocapsid (NC) processing in HIV-1 replication, synthetic oligopeptide substrates representing the wild-type and modified versions of the proximal cleavage site of HIV-1 NC were assayed as substrates of the HIV-1 protease (PR). The S1′ substrate binding site of HIV-1 PR was studied by an in vitro assay using KIVKCF↓NCGK decapeptides having amino acid substitutions of N17 residue of the cleavage site of the first zinc-finger domain, and in silico calculations were also performed to investigate amino acid preferences of S1′ site. Second site substitutions have also been designed to produce “revertant” substrates and convert a non-hydrolysable sequence (having glycine in place of N17) to a substrate. The specificity constants obtained for peptides containing non-charged P1′ substitutions correlated well with the residue volume, while the correlation with the calculated interaction energies showed the importance of hydrophobicity: interaction energies with polar residues were related to substantially lower specificity constants. Cleavable “revertants” showed one residue shift of cleavage position due to an alternative productive binding mode, and surprisingly, a double cleavage of a substrate was also observed. The results revealed the importance of alternative binding possibilities of substrates into the HIV-1 PR. The introduction of the “revertant” mutations into infectious virus clones may provide further insights into the potential role of NC processing in the early phase of the viral life-cycle.

Microradiographic Anatomy of the Explanted Rat Colon

1995 ◽  
Vol 36 (2) ◽  
pp. 210-214 ◽  
Author(s):  
F. Pomerri ◽  
G. Gasparini ◽  
A. Martin ◽  
W. Fries ◽  
E. Pagiaro ◽  
...  
Keyword(s):  
Distal Colon ◽  
Proximal Colon ◽  
Rat Colon ◽  
Sprague Dawley ◽  
Double Contrast ◽  
Colonic Wall ◽  
Sprague Dawley Rats ◽  
Contrast Technique ◽  
Isolated Aorta ◽  
Mucosal Folds

The colon of 32 healthy Sprague-Dawley rats was studied microradiographically. The colonic arterial distribution of 18 rats was examined after injecting barium sulfate into the isolated aorta. The mucosal surface in 9 rats was studied using double-contrast technique after colon explantation. In 5 animals arterial and mucosal studies were carried out simultaneously. The radiographic thickness of the colonic wall was measured using a comparative microscope. The specimens were observed, photographed and examined histologically. Unlike the cecum and distal colon which, when insufflated, do not have mucosal folds, the proximal colon exhibits folds in an oblique direction corresponding to that of the arteries, and the colonic wall in this region is thicker. Comparison between arterial and mucosal microradiographic anatomy and wall thickness enables the proposition of a simple nontopographic division of the rat colon into cecum, proximal colon and distal colon.

Postnatal development of colonic electrolyte transport in rabbits

1990 ◽  
Vol 258 (3) ◽  
pp. G447-G453 ◽  
Author(s):  
E. V. O'Loughlin ◽  
D. M. Hunt ◽  
D. Kreutzmann
Keyword(s):  
Chloride Transport ◽  
Age Groups ◽  
Serum Cortisol ◽  
Distal Colon ◽  
Proximal Colon ◽  
Transport Studies ◽  
Age Related ◽  
Serum Aldosterone ◽  
Group Transport

Postnatal changes in adrenal gluco- and mineralocorticoid secretion and colonic sodium and chloride transport were examined. New Zealand White rabbits, age 10-14, 18-22, and 25-30 days, and adult animals (6-10 wk) were studied. Serum cortisol, corticosterone, aldosterone, and mucosal Na(+)-K(+)-ATPase activities were measured in each age group. Transport studies were performed in vitro under short-circuited conditions in distal colon at all age groups and in proximal colon in days 10-14 and 18-22 and in adult animals. Serum glucocorticoids varied little until after day 30 when they rose to adult levels. On the other hand, serum aldosterone levels were two- to threefold higher in days 10-14 and 18-22 animals but fell to adult levels by day 25. In distal colon, amiloride-inhibitable electrogenic Na+ absorption was present at all ages but was significantly greater (P less than 0.01) in days 10-14 (3.8 +/- 0.5 mu eq.cm-2.h-1) and 18-22 (4.2 +/- 0.4) rabbits compared with adults (1.9 +/- 0.4) but not day 25-30 (2.8 +/- 0.5). In proximal colon, Na+ absorption was significantly higher (P less than 0.05) in day 10-14 (1.6 +/- 0.5 mu eq.cm-2.h-1) compared with day 18-22 (-0.2 +/- 0.5) and adults (0.06 +/- 0.5) and was amiloride insensitive. Neither chloride transport nor mucosal Na(+)-K(+)-ATPase demonstrated significant age-related changes in either region of colon. These results indicate that both proximal and distal colonic Na+ transport undergoes postnatal changes. In distal but not proximal colon these changes appear to be regulated by circulating aldosterone probably by increasing apical membrane permeability to Na+.

scholarly journals High Expression of GSDMC Is Associated with Poor Survival in Kidney Clear Cell Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yun-Qian Cui ◽  
Fei Meng ◽  
Wen-Li Zhan ◽  
Zhou-Tong Dai ◽  
Xinghua Liao
Keyword(s):  
Potential Role ◽  
Clear Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
High Expression ◽  
Poor Survival ◽  
Free Survival

This study is aimed at exploring the potential role of GSDMC in kidney renal clear cell carcinoma (KIRC). We analyzed the expression of GSDMC in 33 types of cancers in TCGA database. The results showed that the expression of GSDMC was upregulated in most cancers. We found a significant association between high expression of GSDMC and shortened patient overall survival, progression-free survival, and disease-specific survival. In vitro experiments have shown that the expression of GSDMC was significantly elevated in KIRC cell lines. Moreover, decreased expression of GSDMC was significantly associated with decreased cell proliferation. In summary, we believe that this study provides valuable data supporting future clinical treatment.

scholarly journals Autophagy and Age-Related Eye Diseases

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Xue Yang ◽  
Xinan Pan ◽  
Xiaorui Zhao ◽  
Jin Luo ◽  
Mingpu Xu ◽  
...  
Keyword(s):  
Eye Diseases ◽  
Regulatory Function ◽  
Ocular Diseases ◽  
Potential Therapeutic Target ◽  
Age Related ◽  
Different Types ◽  
Survival And Development ◽  
Catabolic Process

Background. Autophagy is a catabolic process that depends on the lysosome. It is usually used to maintain cellular homeostasis, survival and development by degrading abnormal substances and dysfunctional organelles, especially when the cell is exposed to starvation or other stresses. Increasing studies have reported that autophagy is associated with various eye diseases, of which aging is one of the important factors. Objective. To summarize the functional and regulatory role of autophagy in ocular diseases with aging, and discuss the possibility of autophagy-targeted therapy in age-related diseases. Methods. PubMed searches were performed to identify relevant articles published mostly in the last 5 years. The key words were used to retrieve including “autophagy”, “aging”, “oxidative stress AND autophagy”, “dry eye AND autophagy”, “corneal disease AND autophagy”, “glaucoma AND autophagy”, “cataract AND autophagy”, “AMD AND autophagy”, “cardiovascular diseases AND autophagy”, “diabetes AND autophagy”. After being classified and assessed, the most relevant full texts in English were chosen. Results. Apart from review articles, more than two research articles for each age-related eye diseases related to autophagy were retrieved. We only included the most relevant and recent studies for summary and discussion. Conclusion. Autophagy has both protective and detrimental effects on the progress of age-related eye diseases. Different types of studies based on certain situations in vitro showed distinct results, which do not necessarily coincide with the actual situation in human bodies completely. It means the exact role and regulatory function of autophagy in ocular diseases remains largely unknown. Although autophagy as a potential therapeutic target has been proposed, many problems still need to be solved before it applies to clinical practice.

scholarly journals Ozone Therapy as Adjuvant for Cancer Treatment: Is Further Research Warranted?

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Bernardino Clavo ◽  
Norberto Santana-Rodríguez ◽  
Pedro Llontop ◽  
Dominga Gutiérrez ◽  
Gerardo Suárez ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Immune Modulation ◽  
Animal Studies ◽  
Potential Role ◽  
Randomized Clinical Trials ◽  
Tumor Hypoxia ◽  
Tumor Resection ◽  
Ozone Therapy

Introduction. This article provides an overview of the potential use of ozone as an adjuvant during cancer treatment.Methods. We summarize the findings of the most relevant publications focused on this goal, and we include our related clinical experience.Results. Over several decades, prestigious journals have publishedin vitrostudies on the capacity of ozone to induce direct damage on tumor cells and, as well, to enhance the effects of radiotherapy and chemotherapy. Indirect effects have been demonstrated in animal models: immune modulation by ozone alone and sensitizing effect of radiotherapy by concurrent ozone administration. The effects of ozone in modifying hemoglobin dissociation curve, 2,3-diphosphoglycerate levels, locoregional blood flow, and tumor hypoxia provide additional support for potential beneficial effects during cancer treatment. Unfortunately, only a few clinical studies are available. Finally, we describe some works and our experience supporting the potential role of local ozone therapy in treating delayed healing after tumor resection, to avoid delays in commencing radiotherapy and chemotherapy.Conclusions.In vitroand animal studies, as well as isolated clinical reports, suggest the potential role of ozone as an adjuvant during radiotherapy and/or chemotherapy. However, further research, such as randomized clinical trials, is required to demonstrate its potential usefulness as an adjuvant therapeutic tool.

Neural regulation of in vitro giant contractions in the rat colon

2001 ◽  
Vol 281 (1) ◽  
pp. G275-G282 ◽  
Author(s):  
Asensio Gonzalez ◽  
Sushil K. Sarna
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Sch 23390 ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Muscle Cells ◽  
Enteric Neurons ◽  
Rat Colon ◽  
Spontaneous Contractions

The rat middle colon spontaneously generates regularly occurring giant contractions (GCs) in vitro. We investigated the neurohumoral and intracellular regulation of these contractions in a standard muscle bath. cGMP content was measured in strips and single smooth muscle cells. The circular muscle strips generated spontaneous GCs. Their amplitude and frequency were significantly increased by tetrodotoxin (TTX), ω-conotoxin, N ω-nitro-l-arginine (l-NNA), and the dopamine D1 receptor antagonist Sch-23390. The GCs were unaffected by hexamethonium, atropine, and antagonists of serotonergic (5-HT1–4), histaminergic (H1–2), and tachykininergic (NK1–2) receptors but enhanced by NK3receptor antagonism. The guanylate cyclase inhibitor 1H-[1,2,4]oxidiazolo[4,3-a]quinoxalin-1-one (ODQ) also enhanced GCs to the same extent as TTX and l-NNA, and each of the three agents prevented the effects of the others. GCs were abolished by electrical field stimulation, S-nitroso- N-acetyl-penicillamine, and 8-bromo-cGMP. BAY-K-8644 and apamin enhanced the GCs, but they were abolished by D-600. Basal cGMP content in strips was decreased by TTX,l-NNA, or ODQ, but these treatments had no effect on cGMP content of enzymatically dissociated single smooth muscle cells. We conclude that spontaneous contractions in the rat colonic muscle strips are not generated by cholinergic, serotonergic, or histaminergic input. Constitutive release of nitric oxide from enteric neurons sustains cGMP synthesis in the colonic smooth muscle to suppress spontaneous in vitro GCs.

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