scholarly journals Is the mechanism of nitroglycerin tolerance associated with aldehyde dehydrogenase activity? A contribution to the ongoing discussion

2019 ◽  
Author(s):  
Anna Bilska-Wilkosz ◽  
Magdalena Kotańska ◽  
Magdalena Górny ◽  
Barbara Filipek ◽  
Małgorzata Iciek
Keyword(s):  
Rat Liver ◽  
Aldehyde Dehydrogenase ◽  
Lipoic Acid ◽  
Total Activity ◽  
Nitrate Tolerance ◽  
Aldh Activity ◽  
Liver Homogenates ◽  
Development Of Tolerance ◽  
Aldehyde Dehydrogenase Activity

The aim of the study presented here was an attempt to answer the question posed in the title: Is the mechanism of nitroglycerin tolerance associated with aldehyde dehydrogenase (ALDH) activity? Here, we investigated the effect of administration (separately or jointly) of lipoic acid (LA), nitroglycerin (GTN), and disulfiram (DSF; an irreversible in vivo inhibitor of all ALDH isozymes (including ALDH2)), on the development of tolerance to GTN. We also assessed the total activity of ALDH in the rat liver homogenates. Our data revealed that not only DSF and GTN inhibited the total ALDH activity in the rat liver, but LA also proved to be an inhibitor of this enzyme. At the same time, the obtained results demonstrated that the GTN tolerance did not develop in GTN, DSF and LA jointly treated rats, but did develop in GTN and DSF jointly treated rats. This means that the ability of LA to prevent GTN tolerance is not associated with the total ALDH activity in the rat liver. In this context, the fact that animals jointly receiving GTN and DSF developed tolerance to GTN, and in animals that in addition to GTN and DSF also received LA such tolerance did not develop, is – in our opinion – a sufficient premise to conclude that the nitrate tolerance certainly is not caused by a decrease in the activity of any of the ALDH isoenzymes present in the rat liver, including ALDH2. However, many questions still await an answer, including the basic one: What is the mechanism of tolerance to nitroglycerin?

scholarly journals Intracellular localization of aldehyde dehydrogenase in rat liver

1972 ◽  
Vol 127 (4) ◽  
pp. 633-639 ◽  
Author(s):  
Leo Marjanen
Keyword(s):  
Rat Liver ◽  
Aldehyde Dehydrogenase ◽  
Gradient Centrifugation ◽  
Intracellular Localization ◽  
Total Activity ◽  
Mitochondrial Fraction ◽  
Point Of View ◽  
Ethanol Metabolism ◽  
Acetaldehyde Oxidation

1. Distribution of aldehyde dehydrogenase activity in rat liver was studied by measuring the rate of disappearance of acetaldehyde in the presence of each of the subcellular fractions. These were obtained by rough separation of particulate fractions from the soluble portion of the cell, by differential centrifugation, and by isopycnic gradient centrifugation. 2. The maximal rate of acetaldehyde oxidation was 3.7 μmol/min per g, with an apparent Km value below 10-5m. The highest rate of activity was observed in phosphate buffers of high Pi concentration (above 60mm). 3. The activity measured was completely dependent on NAD+. 4. The microsomal fraction and the nuclei were inactive in the assay. Of the total activity 80% was found in the mitochondrial fraction and the remaining 20% in the cytoplasm. 5. The distribution pattern is important from the point of view of acetaldehyde oxidation during ethanol metabolism. The apparent discrepancy of the results obtained by different workers and the localization of acetaldehyde oxidation in vivo is discussed.

scholarly journals Antifibrotic effect of lung-resident progenitor cells with high aldehyde dehydrogenase activity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hiroshi Takahashi ◽  
Taku Nakashima ◽  
Takeshi Masuda ◽  
Masashi Namba ◽  
Shinjiro Sakamoto ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Aldehyde Dehydrogenase ◽  
Cell Populations ◽  
Aldh Activity ◽  
Aged Mice ◽  
Effects Of Aging ◽  
Aldehyde Dehydrogenase Activity

Abstract Background Aldehyde dehydrogenase (ALDH) is highly expressed in stem/progenitor cells in various tissues, and cell populations with high ALDH activity (ALDHbr) are associated with tissue repair. However, little is known about lung-resident ALDHbr. This study was performed to clarify the characteristics of lung-resident ALDHbr cells and to evaluate their possible use as a tool for cell therapy using a mouse model of bleomycin-induced pulmonary fibrosis. Methods The characteristics of lung-resident/nonhematopoietic (CD45−) ALDHbr cells were assessed in control C57BL/6 mice. The kinetics and the potential usage of CD45−/ALDHbr for cell therapy were investigated in bleomycin-induced pulmonary fibrosis. Localization of transferred CD45−/ALDHbr cells was determined using mCherry-expressing mice as donors. The effects of aging on ALDH expression were also assessed using aged mice. Results Lung CD45−/ALDHbr showed higher proliferative and colony-forming potential than cell populations with low ALDH activity. The CD45−/ALDHbr cell population, and especially its CD45−/ALDHbr/PDGFRα+ subpopulation, was significantly reduced in the lung during bleomycin-induced pulmonary fibrosis. Furthermore, mRNA expression of ALDH isoforms was significantly reduced in the fibrotic lung. When transferred in vivo into bleomycin-pretreated mice, CD45−/ALDHbr cells reached the site of injury, ameliorated pulmonary fibrosis, recovered the reduced expression of ALDH mRNA, and prolonged survival, which was associated with the upregulation of the retinol-metabolizing pathway and the suppression of profibrotic cytokines. The reduction in CD45−/ALDHbr/PDGFRα+ population was more remarkable in aged mice than in young mice. Conclusions Our results strongly suggest that the lung expression of ALDH and lung-resident CD45−/ALDHbr cells are involved in pulmonary fibrosis. The current study signified the possibility that CD45−/ALDHbr cells could find application as novel and useful cell therapy tools in pulmonary fibrosis treatment.

scholarly journals Can Lipoic Acid Attenuate Cardiovascular Disturbances Induced by Ethanol and Disulfiram Administration Separately or Jointly in Rats?

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Anna Bilska-Wilkosz ◽  
Magdalena Kotańska ◽  
Magdalena Górny ◽  
Barbara Filipek ◽  
Małgorzata Iciek
Keyword(s):  
Blood Pressure ◽  
Rat Liver ◽  
Lipoic Acid ◽  
Aldh Activity ◽  
Dihydrolipoic Acid ◽  
Treatment Groups ◽  
Intracellular Compartments ◽  
Electrocardiogram Ecg ◽  
First Time ◽  
All Treatment

The exogenous lipoic acid (LA) is successfully used as a drug in the treatment of many diseases. It is assumed that after administration, LA is transported to the intracellular compartments and reduced to dihydrolipoic acid (DHLA) which is catalyzed by NAD(P)H-dependent enzymes. The purpose of this study was to investigate whether LA can attenuate cardiovascular disturbances induced by ethanol (EtOH) and disulfiram (DSF) administration separately or jointly in rats. For this purpose, we measured systolic and diastolic blood pressure, recorded electrocardiogram (ECG), and estimated mortality of rats. We also studied the activity of aldehyde dehydrogenase (ALDH) in the rat liver. It was shown for the first time that LA partially attenuated the cardiac arrhythmia (extrasystoles and atrioventricular blocks) induced by EtOH and reduced the EtOH-induced mortality of animals, which suggests that LA may have a potential for use in cardiac disturbance in conditions of acute EtOH intoxication. The administration of EtOH, LA, and DSF separately or jointly affected the ALDH activity in the rat liver since a significant decrease in the activity of the enzyme was observed in all treatment groups. The results indicating that LA is an inhibitor of ALDH activity are very surprising.

Aldehyde dehydrogenase activity in serous ovarian carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15577-e15577
Author(s):  
Petra M. Bareiss ◽  
Tanja N. Fehm ◽  
Anna Fischer ◽  
Matthias Grauer ◽  
Philipp Kokorsch ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Ovarian Carcinoma ◽  
Aldehyde Dehydrogenase ◽  
Cell Cycle Distribution ◽  
Aldh Activity ◽  
Serous Ovarian Carcinoma ◽  
Aldh1 Expression

e15577 Background: Only specific subpopulations of tumor cells, so called cancer stem cells (CSC) may initiate and maintain tumors. The phenotype and molecular properties of ovarian CSC remain elusive. Aldehyde dehydrogenase (ALDH) activity characterizes (cancer) stem cells in different tissues and has been associated with ovarian CSC (Silva et al, 2011; Kryczek et al, 2012). Contradictory results have been reported on ALDH1 expression and prognosis in ovarian carcinoma. In this study, we explore the role of ALDH in serous ovarian carcinoma (SOC). Methods: Aldefluor-staining was used to assess ALDH activity in different ovarian carcinoma cell-lines and patient samples. ALDH+ and ALDH- cells isolated by FACS and ALDH1 versus control siRNA treated cells were analyzed in sphere forming, proliferation, BrdU and cell cycle assays. In vivo tumorigenicity assays including serial re-transplantations were performed in NOD/SCID/IL2Rγnull mice. ALDH1 and Ki67 expression were assessed immunohistochemically on a tissue microarray of 152 SOC samples. Results: ALDH+ cells formed more tumor spheres than ALDH- cells from the OVCAR-3 cell line and primary SOC and larger spheres (> 5.000 µm²) developed solely from ALDH+ cells. However, in vivo both cell fractions gave rise to tumors. Tumors contained both ALDH+ and ALDH- cells irrespective of the starting population. Notably, ALDH+ cells generated tumors more rapidly and induced larger tumors, suggesting a higher proliferative capacity. Immunohistochemical analysis of a larger cohort of SOC patients confirmed association of ALDH1 expression with the proliferation marker Ki67 (p=0.007). Surprisingly, co-stainings revealed that ALDH1 positive cells were mostly Ki67 negative and cell cycle synchronisation experiments using different agents showed ALDH induction in G0-enriched OVCAR-3 cells. However, inhibition of ALDH by treatment with three distinct siRNAs against ALDH1 did not alter cell cycle distribution. Conclusions: Our data suggest that ALDH is a correlative marker indicating, but not actively sustaining a quiescent stem-cell like state in SOC. Upon exit from G0, ALDH+ cells lose ALDH expression and induce a proliferative response.

Optimized Spectrophotometric Determination of Aldehyde Dehydrogenase Activity in Erythrocytes

1992 ◽  
Vol 38 (4) ◽  
pp. 584-588 ◽  
Author(s):  
R D Johnson ◽  
J Bahnisch ◽  
B Stewart ◽  
D J Shearman ◽  
J B Edwards
Keyword(s):  
Alcohol Consumption ◽  
Dehydrogenase Activity ◽  
Aldehyde Dehydrogenase ◽  
Biological Marker ◽  
Aldh Activity ◽  
Lactate Dehydrogenase Activity ◽  
Analytical Imprecision ◽  
Excess Alcohol Consumption ◽  
Aldehyde Dehydrogenase Activity

Abstract We describe a reliable and sensitive semiautomated spectrophotometric assay of aldehyde dehydrogenase (ALDH; EC 1.2.1.3) activity in erythrocytes. The hemolysate can be stabilized with sucrose, and the technique involves only microliters of hemolysate on a centrifugal analyzer. The use of microcolumns to remove interfering hemoglobin is avoided, and reproducibility of the assay has been improved by manipulating the inherent lactate dehydrogenase activity of erythrocytes by adding lactate and oxalate to the reaction mixture. These modifications have decreased the analytical imprecision of the assay, allowing a better appraisal of aldehyde dehydrogenase activity in erythrocytes as a biological marker of excess alcohol consumption. Erythrocytic ALDH activity was significantly less in 40 alcoholics than in 145 teetotallers (median activity 128 vs 219 mU/g of hemoglobin, respectively; P = 0.0001), indicating the potential of this assay as a useful marker of excess alcohol consumption.

scholarly journals Characterization of Cardiac-Resident Progenitor Cells Expressing High Aldehyde Dehydrogenase Activity

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Marc-Estienne Roehrich ◽  
Albert Spicher ◽  
Giuseppina Milano ◽  
Giuseppe Vassalli
Keyword(s):  
Progenitor Cells ◽  
Aldehyde Dehydrogenase ◽  
Preclinical Studies ◽  
Cell Passage ◽  
Aldh Activity ◽  
Human Cord Blood ◽  
Angiogenic Activity ◽  
Stem And Progenitor Cells ◽  
Aldehyde Dehydrogenase Activity

High aldehyde dehydrogenase (ALDH) activity has been associated with stem and progenitor cells in various tissues. Human cord blood and bone marrow ALDH-bright (ALDHbr) cells have displayed angiogenic activity in preclinical studies and have been shown to be safe in clinical trials in patients with ischemic cardiovascular disease. The presence of ALDHbrcells in the heart has not been evaluated so far. We have characterized ALDHbrcells isolated from mouse hearts. One percent of nonmyocytic cells from neonatal and adult hearts were ALDHbr. ALDHvery-brcells were more frequent in neonatal hearts than adult. ALDHbrcells were more frequent in atria than ventricles. Expression of ALDH1A1 isozyme transcripts was highest in ALDHvery-brcells, intermediate in ALDHbrcells, and lowest in ALDHdimcells. ALDH1A2 expression was highest in ALDHvery-brcells, intermediate in ALDHdimcells, and lowest in ALDHbrcells. ALDH1A3 and ALDH2 expression was detectable in ALDHvery-brand ALDHbrcells, unlike ALDHdimcells, albeit at lower levels compared with ALDH1A1 and ALDH1A2. Freshly isolated ALDHbrcells were enriched for cells expressing stem cell antigen-1, CD34, CD90, CD44, and CD106. ALDHbrcells, unlike ALDHdimcells, could be grown in culture for more than 40 passages. They expressed sarcomericα-actinin and could be differentiated along multiple mesenchymal lineages. However, the proportion of ALDHbrcells declined with cell passage. In conclusion, the cardiac-derived ALDHbrpopulation is enriched for progenitor cells that exhibit mesenchymal progenitor-like characteristics and can be expanded in culture. The regenerative potential of cardiac-derived ALDHbrcells remains to be evaluated.

Sign in / Sign up

Export Citation Format

Share Document