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2. Omega-3 Fatty Acid Expression Attenuates Chronic Hypoxia-Induced and Smoke-Induced Pulmonary Hypertension

Author

Schaeffer, J., primary, Gierhardt, M., additional, Pak, O., additional, Malkmus, K., additional, Kraut, S., additional, Hadžić, S., additional, Schupp, N., additional, Bonthu, D., additional, Reiche, S., additional, Savai, R., additional, Ghofrani, A., additional, Grimminger, F., additional, Seeger, W., additional, Weissmann, N., additional, Hecker, M., additional, and Sommer, N., additional

Published
2022
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11. Aldosterone activates the oncogenic signals ERK1/2 and STAT3 via redox-regulated mechanisms

Author

Queisser, N, Schupp, N, Schwarz, E, Hartmann, C, Mackenzie, GG, and Oteiza, PI

Subjects
Male, STAT3 Transcription Factor, endocrine system, congenital, hereditary, and neonatal diseases and abnormalities, endocrine system diseases, Oncology and Carcinogenesis, Kidney, Cell Transformation, ERK1, Cell Line, STAT3, Animals, Humans, oxidative stress, Oncology & Carcinogenesis, Aldosterone, Cell Proliferation, Mitogen-Activated Protein Kinase 1, Neoplastic, Mitogen-Activated Protein Kinase 3, ERK1/2, urogenital system, nutritional and metabolic diseases, NADPH Oxidases, kidney cancer, Kidney Neoplasms, Rats, Enzyme Activation, Sprague-Dawley, Nitric Oxide Synthase, Oxidation-Reduction
Abstract

© 2017 Wiley Periodicals, Inc. Epidemiological studies found an increased risk for kidney cancer in hypertensive patients, of which a subgroup has high aldosterone (Ald) levels. We recently showed that Ald is genotoxic both in kidney tubular cells and in rats with mineralocorticoid-mediated hypertension. The present work investigated in vitro and in vivo, if the oxidative stress-mediated activation of the ERK1/2 pathway, and its downstream target STAT3, could be one mechanism involved in the potential oncogenic capability of excess Ald exposure. The effects of excess Ald were investigated in LLC-PK1 cells and in Ald-induced hypertensive rats. Ald caused cRaf, MEK1/2, and ERK1/2 phosphorylation both in LLC-PK1 cells and in rat kidneys. ERK1/2 activation led to an increased phosphorylation of MSK1, p90RSK, and STAT3. The involvement of ERK1/2 in the activation of STAT3 was evidenced by the capacity of the MEK inhibitor U0126 to prevent Ald-mediated ERK1/2 and STAT3 phosphorylation. Both in vitro and in vivo, the activation of ERK1/2 and STAT3 by Ald was dependent on the mineralocorticoid receptor and was triggered by an increase in cellular oxidants. Ald-mediated oxidant increase was in part due to the activation of the enzymes NADPH oxidase and NO synthase. Proliferation was significantly enhanced and apoptosis decreased in Ald-treated rat kidneys and/or LLC-PK1 cells. Results support the concept that the oxidant-mediated long-term activation of ERK1/2/STAT3 by persistently high Ald levels could trigger proliferative and prosurvival events. Ald-mediated promotion of cell survival and DNA damage could result in kidney cell transformation and initiation of cancer in hypertensive patients with hyperaldosteronism.

Published
2017

14. Surgical Decompression is a Prerequisite for the Beneficial Effect of Statin Therapy in Renal Ischemia-Reperfusion Injury

Author

Wagner, A, Schupp, N, Wang, H, Bartenstein, P, Hacker, M, Jauch, KW, Guba, M, and Herrler, T

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Introduction: The aim of this study is to determine the effect of statins alone and in combination with microcapsulotomy on renal ischemia-reperfusion (I/R) injury. As chronic inflammatory reactions predispose to fibrosis and dysfunction, the impact on macrophages as the characteristic cell type[for full text, please go to the a.m. URL], 130. Kongress der Deutschen Gesellschaft für Chirurgie

Published
2013
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16. Aktiv-spezifische Tumorvakzinierung im Rahmen einer Lymphopenie-induzierten Lymphozytenproliferation und Rekonstitution (LRAST) führt zur Induktion therapeutisch wirksamer T-Zellen im murinen Magenkarzinom Modell

Author

van den Engel, N, Rusan, M, Assmann, I, Rüttinger, D, Schupp, N, Meimarakis, G, Zimmermann, W, Hatz, R, and Winter, H

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Die aktiv-spezifische Immuntherapie nach Lymphopenieinduktion und anschließender Immunrekonstitution (LRAST) ist eine vielversprechende neue Immuntherapie zur Induktion tumorspezifischer, therapeutischer T-Zellen. Die Bedeutung dieses Therapieansatzes haben wir in einem murinen Magentumormodell[for full text, please go to the a.m. URL], 127. Kongress der Deutschen Gesellschaft für Chirurgie

Published
2010
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17. Genotoxicity of the neurotransmitter dopamine in vitro

Author

Stopper, H, Schupp, N, Fazeli, G, Dietel, B, Queisser, N, Walitza, S, Gerlach, M, University of Zurich, and Stopper, H

Subjects
3005 Toxicology, 610 Medicine & health, 10058 Department of Child and Adolescent Psychiatry
Published
2009

30. Experimental pathology

Author

Yi Chun, D. X., primary, Alexandre, H., additional, Edith, B., additional, Nacera, O., additional, Julie, P., additional, Chantal, J., additional, Eric, R., additional, Zhang, X., additional, Jin, Y., additional, Miravete, M., additional, Dissard, R., additional, Klein, J., additional, Gonzalez, J., additional, Caubet, C., additional, Pecher, C., additional, Pipy, B., additional, Bascands, J.-L., additional, Mercier-Bonin, M., additional, Schanstra, J., additional, Buffin-Meyer, B., additional, Claire, R., additional, Rigothier, C., additional, Richard, D., additional, Sebastien, L., additional, Moin, S., additional, Chantal, B., additional, Christian, C., additional, Jean, R., additional, Migliori, M., additional, Cantaluppi, V., additional, Mannari, C., additional, Medica, D., additional, Giovannini, L., additional, Panichi, V., additional, Goldwich, A., additional, Alexander, S., additional, Andre, G., additional, Amann, K., additional, Migliorini, A., additional, Sagrinati, C., additional, Angelotti, M. L., additional, Mulay, S. R., additional, Ronconi, E., additional, Peired, A., additional, Romagnani, P., additional, Anders, H.-J., additional, Chiang, W. C., additional, Lai, C. F., additional, Peng, W.-H., additional, Wu, C. F., additional, Chang, F.-C., additional, Chen, Y.-T., additional, Lin, S.-L., additional, Chen, Y. M., additional, Wu, K. D., additional, Lu, K.-S., additional, Tsai, T. J., additional, Virgine, O., additional, Qing Feng, F., additional, Zhang, S.-Y., additional, Dominique, D., additional, Vincent, A., additional, Marina, C., additional, Philippe, L., additional, Georges, G., additional, Pawlak, A., additional, Sahali, D., additional, Matsumoto, S., additional, Kiyomoto, H., additional, Ichimura, A., additional, Dan, T., additional, Nakamichi, T., additional, Tsujita, T., additional, Akahori, K., additional, Ito, S., additional, Miyata, T., additional, Xie, S., additional, Zhang, B., additional, Shi, W., additional, Yang, Y., additional, Nagasu, H., additional, Satoh, M., additional, Kidokoro, K., additional, Nishi, Y., additional, Ihoriya, C., additional, Kadoya, H., additional, Sasaki, T., additional, Kashihara, N., additional, Wu, C.-F., additional, Chou, Y.-H., additional, Duffield, J., additional, Rocca, C., additional, Gregorini, M., additional, Corradetti, V., additional, Valsania, T., additional, Bedino, G., additional, Bosio, F., additional, Pattonieri, E. F., additional, Esposito, P., additional, Sepe, V., additional, Libetta, C., additional, Rampino, T., additional, Dal Canton, A., additional, Omori, H., additional, Kawada, N., additional, Inoue, K., additional, Ueda, Y., additional, Yamamoto, R., additional, Matsui, I., additional, Kaimori, J., additional, Takabatake, Y., additional, Moriyama, T., additional, Isaka, Y., additional, Rakugi, H., additional, Wasilewska, A., additional, Taranta-Janusz, K., additional, Deebek, W., additional, Kuroczycka-Saniutycz, E., additional, Lee, A. S., additional, Lee, J. E., additional, Jung, Y. J., additional, Kang, K. P., additional, Lee, S., additional, Kim, W., additional, Arfian, N., additional, Emoto, N., additional, Yagi, K., additional, Nakayama, K., additional, Hartopo, A. B., additional, Nugrahaningsih, D. A., additional, Yanagisawa, M., additional, Hirata, K.-I., additional, Munoz-Felix, J. M., additional, Lopez-Novoa, J. M., additional, Martinez-Salgado, C., additional, Oujo, B., additional, Arevalo, M., additional, Bernabeu, C., additional, Perez-Barriocanal, F., additional, Jesper, K., additional, Nathalie, V., additional, Pierre, G., additional, Yi Chun, D. X., additional, Iyoda, M., additional, Shibata, T., additional, Matsumoto, K., additional, Shindo-Hirai, Y., additional, Kuno, Y., additional, Wada, Y., additional, Akizawa, T., additional, Schwartz, I., additional, Schwartz, D., additional, Prot Bertoye, C., additional, Terryn, S., additional, Claver, J., additional, Beghdadi, W. B., additional, Monteiro, R., additional, Blank, U., additional, Devuyst, O., additional, Daugas, E., additional, Van Beneden, K., additional, Geers, C., additional, Pauwels, M., additional, Mannaerts, I., additional, Van den Branden, C., additional, Van Grunsven, L. A., additional, Seckin, I., additional, Pekpak, M., additional, Uzunalan, M., additional, Uruluer, B., additional, Kokturk, S., additional, Ozturk, Z., additional, Sonmez, H., additional, Yaprak, E., additional, Furuno, Y., additional, Tsutsui, M., additional, Morishita, T., additional, Shimokawa, H., additional, Otsuji, Y., additional, Yanagihara, N., additional, Kabashima, N., additional, Ryota, S., additional, Kanegae, K., additional, Miyamoto, T., additional, Nakamata, J., additional, Ishimatsu, N., additional, Tamura, M., additional, Nakagawa, T., additional, Ichikawa, K., additional, Miyamoto, M., additional, Takabayashi, D., additional, Yamazaki, H., additional, Kakeshita, K., additional, Koike, T., additional, Kagitani, S., additional, Tomoda, F., additional, Hamashima, T., additional, Ishii, Y., additional, Inoue, H., additional, Sasahara, M., additional, El Machhour, F., additional, Kerroch, M., additional, Mesnard, L., additional, Chatziantoniou, C., additional, Dussaule, J.-C., additional, Inui, K., additional, Sasai, F., additional, Maruta, Y., additional, Nishiwaki, H., additional, Kawashima, E., additional, Inoue, Y., additional, Yoshimura, A., additional, Musacchio, E., additional, Priante, G., additional, Valvason, C., additional, Sartori, L., additional, Baggio, B., additional, Kim, J. H., additional, Gross, O., additional, Diana, R., additional, Gry, D. H., additional, Asimal, B., additional, Johanna, T., additional, Imke, S.-E., additional, Lydia, W., additional, Gerhard-Anton, M., additional, Hassan, D., additional, Cano, J. L., additional, Griera, M., additional, Olmos, G., additional, Martin, P., additional, Cortes, M. A., additional, Lopez-Ongil, S., additional, Rodriguez-Puyol, D., additional, DE Frutos, S., additional, Gonzalez, M., additional, Luengo, A., additional, Rodriguez-Puyol, M., additional, Calleros, L., additional, Lupica, R., additional, Lacquaniti, A., additional, Donato, V., additional, Maggio, R., additional, Mastroeni, C., additional, Lucisano, S., additional, Cernaro, V., additional, Fazio, M. R., additional, Quartarone, A., additional, Buemi, M., additional, Kacik, M., additional, Goedicke, S., additional, Eggert, H., additional, Hoyer, J. D., additional, Wurm, S., additional, Steege, A., additional, Banas, M., additional, Kurtz, A., additional, Banas, B., additional, Lasagni, L., additional, Lazzeri, E., additional, Romoli, S., additional, Schaefer, I., additional, Teng, B., additional, Worthmann, K., additional, Haller, H., additional, Schiffer, M., additional, Prattichizzo, C., additional, Netti, G. S., additional, Rocchetti, M. T., additional, Cormio, L., additional, Carrieri, G., additional, Stallone, G., additional, Grandaliano, G., additional, Ranieri, E., additional, Gesualdo, L., additional, Kucher, A., additional, Smirnov, A., additional, Parastayeva, M., additional, Beresneva, O., additional, Kayukov, I., additional, Zubina, I., additional, Ivanova, G., additional, Abed, A., additional, Schlekenbach, L., additional, Foglia, B., additional, Kwak, B., additional, Chadjichristos, C., additional, Queisser, N., additional, Schupp, N., additional, Brand, S., additional, Himer, L., additional, Szebeni, B., additional, Sziksz, E., additional, Saijo, S., additional, Kis, E., additional, Prokai, A., additional, Banki, N. F., additional, Fekete, A., additional, Tulassay, T., additional, Vannay, A., additional, Hegner, B., additional, Schaub, T., additional, Lange, C., additional, Dragun, D., additional, Klinkhammer, B. M., additional, Rafael, K., additional, Monika, M., additional, Anna, M., additional, Van Roeyen, C., additional, Boor, P., additional, Eva Bettina, B., additional, Simon, O., additional, Esther, S., additional, Floege, J., additional, Kunter, U., additional, Janke, D., additional, Jankowski, J., additional, Hayashi, M., additional, Takamatsu, I., additional, Horimai, C., additional, Yoshida, T., additional, Seno DI Marco, G., additional, Koenig, M., additional, Stock, C., additional, Reiermann, S., additional, Amler, S., additional, Koehler, G., additional, Fobker, M., additional, Buck, F., additional, Pavenstaedt, H., additional, Lang, D., additional, Brand, M., additional, Plotnikov, E., additional, Morosanova, M., additional, Pevzner, I., additional, Zorova, L., additional, Pulkova, N., additional, Zorov, D., additional, Wornle, M., additional, Ribeiro, A., additional, Belling, F., additional, Merkle, M., additional, Nakazawa, D., additional, Nishio, S., additional, Shibasaki, S., additional, Tomaru, U., additional, Akihiro, I., additional, Kobayashi, I., additional, Imanishi, Y., additional, Kurajoh, M., additional, Nagata, Y., additional, Yamagata, M., additional, Emoto, M., additional, Michigami, T., additional, Ishimura, E., additional, Inaba, M., additional, Wu, C.-C., additional, Lu, K.-C., additional, Chen, J.-S., additional, Chu, P., additional, Lin, Y.-F., additional, Eller, K., additional, Schroll, A., additional, Kirsch, A., additional, Huber, J., additional, Weiss, G., additional, Theurl, I., additional, Rosenkranz, A. R., additional, Zawada, A., additional, Rogacev, K., additional, Achenbach, M., additional, Fliser, D., additional, Held, G., additional, Heine, G. H., additional, Miyamoto, Y., additional, Iwao, Y., additional, Watanabe, H., additional, Kadowaki, D., additional, Ishima, Y., additional, Chuang, V. T. G., additional, Sato, K., additional, Otagiri, M., additional, Maruyama, T., additional, Iwatani, H., additional, Honda, D., additional, Noguchi, T., additional, Tanaka, M., additional, Tanaka, H., additional, Fukagawa, M., additional, Pircher, J., additional, Koppel, S., additional, Mannell, H., additional, Krotz, F., additional, Virzi, G. M., additional, Bolin, C., additional, Cruz, D., additional, Scalzotto, E., additional, De Cal, M., additional, Vescovo, G., additional, Ronco, C., additional, Grobmayr, R., additional, Lech, M., additional, Ryu, M., additional, Aoshima, Y., additional, Mizobuchi, M., additional, Ogata, H., additional, Kumata, C., additional, Nakazawa, A., additional, Kondo, F., additional, Ono, N., additional, Koiwa, F., additional, Kinugasa, E., additional, Freisinger, W., additional, Lale, N., additional, Lampert, A., additional, Ditting, T., additional, Heinlein, S., additional, Schmieder, R. E., additional, Veelken, R., additional, Nave, H., additional, Perthel, R., additional, Suntharalingam, M., additional, Bode-Boger, S., additional, Beutel, G., additional, Kielstein, J., additional, Rodrigues-Diez, R., additional, Rayego-Mateos, S., additional, Lavoz, C., additional, Stark Aroeira, L. G., additional, Orejudo, M., additional, Alique, M., additional, Ortiz, A., additional, Egido, J., additional, Ruiz-Ortega, M., additional, Oskar, W., additional, Rusan, C., additional, Padberg, J.-S., additional, Wiesinger, A., additional, Reuter, S., additional, Grabner, A., additional, Kentrup, D., additional, Lukasz, A., additional, Oberleithner, H., additional, Pavenstadt, H., additional, Kumpers, P., additional, Eberhardt, H. U., additional, Skerka, C., additional, Chen, Q., additional, Hallstroem, T., additional, Hartmann, A., additional, Kemper, M. J., additional, Zipfel, P. F., additional, N'gome-Sendeyo, K., additional, Fan, Q.-F., additional, Toblli, J., additional, Cao, G., additional, Giani, J. F., additional, Dominici, F. P., additional, Kim, J. S., additional, Yang, J. W., additional, Kim, M. K., additional, Han, B. G., additional, and Choi, S. O., additional

Published
2012
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31. AGE-induced genomic damage in kidney tubule cells

Author

Schupp, N, Heidland, A, Scheurich, M, Schinzel, R, Klassen, A, Sebekova, K, Stopper, H, Schupp, N, Heidland, A, Scheurich, M, Schinzel, R, Klassen, A, Sebekova, K, and Stopper, H

Published
2004

41. A two-liquid slag mixing experimental technique for studying the oxidative pre-fuming treatment of lead blast furnace slag.

Author

Deneys A., EPD 1997 Orlando, Florida 09-Feb-9713-Feb-97, Robertson D., Schupp N., Deneys A., EPD 1997 Orlando, Florida 09-Feb-9713-Feb-97, Robertson D., and Schupp N.

Abstract

An experimental technique has been developed for studying the reaction kinetics of the reaction ZnO+2FeO=Zn(g)+Fe2O3, by which zinc evolution can occur from a molten slag bath in the absence of a carbonaceous reductant. Two molten slags were melted independently and then mixed to provide a well defined starting point from which to begin taking measurements. The zinc evolution was largely determined by the quantity of inert gas present to agitate the mixture, but also seemed to be suppressed by some mechanism because the reaction terminated after around 1 hour. A higher lime content suppressed zinc formation; some zinc loss occurred from a high sulphur melt. The reaction was found to be almost certainly temperature dependent., An experimental technique has been developed for studying the reaction kinetics of the reaction ZnO+2FeO=Zn(g)+Fe2O3, by which zinc evolution can occur from a molten slag bath in the absence of a carbonaceous reductant. Two molten slags were melted independently and then mixed to provide a well defined starting point from which to begin taking measurements. The zinc evolution was largely determined by the quantity of inert gas present to agitate the mixture, but also seemed to be suppressed by some mechanism because the reaction terminated after around 1 hour. A higher lime content suppressed zinc formation; some zinc loss occurred from a high sulphur melt. The reaction was found to be almost certainly temperature dependent.

Published
1997

44. Reduction of the genomic damage level in haemodialysis patients by folic acid and vitamin B12 supplementation

Author

Helga Stopper, Udo Bahner, Anna-Teresa Treutlein, Alessandra F. Perna, Andreas Brink, August Heidland, Nicole Schupp, Ursula Schmid, Stopper, H, Treutlein, At, Bahner, U, Schupp, N, Schmid, U, Brink, A, Perna, Alessandra, and Heidland, A.

Subjects
Vitamin, Male, medicine.medical_specialty, Homocysteine, medicine.medical_treatment, Lymphocyte proliferation, Micronuclei, medicine.disease_cause, chemistry.chemical_compound, Folic Acid, Renal Dialysis, Internal medicine, Neoplasms, medicine, Humans, Vitamin B12, Cyanocobalamin, Lymphocytes, Prospective Studies, Dialysis, Aged, Aged, 80 and over, Transplantation, Micronucleus Tests, business.industry, Genome, Human, Dialysi, Middle Aged, Vitamin B 12, Endocrinology, Biochemistry, chemistry, Nephrology, Case-Control Studies, Kidney Failure, Chronic, Female, Hemodialysis, business, Oxidative stress, DNA Damage
Abstract

Background Cancer incidence and genomic damage of peripheral lymphocytes are elevated in patients with end-stage renal failure. Among other uraemic toxins, homocysteine (Hcy) levels are increased in most of these patients. In healthy individuals, plasma Hcy correlates with the degree of genomic damage observed in peripheral blood lymphocytes (PBL). The accumulation of Hcy can be reduced by supplementation with folic acid and vitamin B12. The aim of this study was to analyse whether this supplementation can also lower the genomic damage in PBL of haemodialysis patients. This may ultimately help to reduce cancer incidence in renal patients. Methods In a prospective study with 27 patients, we analysed the genomic damage in dialysis patients before and at different time points after the initiation of folate/vitamin B12 supplementation. Genomic damage was measured by the frequency of micronuclei, a subset of chromosomal aberrations, in PBL. Results Supplementation with folic acid and vitamin B12 (more markedly with both) reduced the micronucleus frequency in PBL of dialysis patients. This was not mediated by altered lymphocyte proliferation capacity or changes in DNA cytosine-methylation. Plasma-Hcy was lowered more efficiently by the combined folic acid/vitamin B12 supplementation, and lymphocyte DNA of this group exhibited a nonsignificant trend for a reduction of 1,N(6)-etheno-2'-deoxyadenosine, a marker for oxidative stress. Conclusions A reduction of the genomic damage in PBL can be achieved in dialysis patients by supplementation with folic acid and vitamin B12. This may be mediated by Hcy reduction.

Published
2008

46. Peroxodicarbonate - a renaissance of an electrochemically generated green oxidizer.

Author

Rücker T, Schupp N, Sprang F, Horsten T, Wittgens B, and Waldvogel SR

Abstract

The direct anodic conversion of alkali carbonates in aqueous media provides access to peroxodicarbonate, which is a safe to use and green oxidizer. Although first reports date back around 150 years, its low concentrations and limited thermal stability have consigned this reagent to oblivion. Boron-doped diamond anodes, novel electrolyser concepts for heat dissipation, and the mixed cation trick allow record breaking peroxodicarbonate concentrations >900 mM. The electrochemical generation of peroxodicarbonate was already demonstrated on a pilot scale. The inherent safety is ensured by the limited stability of the peroxodicarbonate solution, which decomposes under ambient conditions to oxygen and facilitates subsequent downstream processing. This peroxide has, in particular at higher concentrations, an unusual reactivity and seems to be an ideal reagent when peroxo-equivalents in combination with alkaline base are required. The conversions with peroxodicarbonate include the Dakin reaction, epoxidation, oxidation of amines (aliphatic and aromatic) and sulfur compounds, deborolative hydroxylation reactions, and many more. Since the base equivalents also represent the makeup chemical for pulping plants, peroxodicarbonate is an ideal reagent for the selective degradation of lignin to vanillin. Moreover, peroxodicarbonate can be used as a halogen-free bleaching agent. The emerging electrogeneration and use of this green platform oxidizer are surveyed for the first time.

Published
2024
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47. Synthesis of Aromatic N -Oxides Using Electrochemically Generated Peroxodicarbonate.

Author

Kohlpaintner PJ, Schupp N, Ehlenz N, Marquart L, Gooßen LJ, and Waldvogel SR

Abstract

Electrochemically generated green platform oxidizers like peroxodicarbonate (PODIC) constitute a game-changing technology in terms of sustainable chemistry while serving as an alternative counterreaction in the electrochemical hydrogen evolution. Peroxodicarbonate avoids the storage and shipping of concentrated hydrogen peroxide solution. We herein disclose an efficient method for the N -oxidation of quinolines, pyridines, and complex tertiary amines. The use of phenoyloxy succinimide (POSI) is the decisive factor for obtaining N -oxides (28 examples) in isolated yields of up to 98%.

Published
2024
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48. Sensitivity of Human Induced Pluripotent Stem Cells and Thereof Differentiated Kidney Proximal Tubular Cells towards Selected Nephrotoxins.

Author

Mboni-Johnston IM, Kouidrat NMZ, Hirsch C, Weber AG, Meißner A, Adjaye J, and Schupp N

Subjects
Humans, Cell Differentiation, Kidney, Albumins, Epithelial Cells, Induced Pluripotent Stem Cells
Abstract

Proximal tubular epithelial cells (PTEC) are constantly exposed to potentially toxic metabolites and xenobiotics. The regenerative potential of the kidney enables the replacement of damaged cells either via the differentiation of stem cells or the re-acquisition of proliferative properties of the PTEC. Nevertheless, it is known that renal function declines, suggesting that the deteriorated cells are not replaced by fully functional cells. To understand the possible causes of this loss of kidney cell function, it is crucial to understand the role of toxins during the regeneration process. Therefore, we investigated the sensitivity and function of human induced pluripotent stem cells (hiPSC), hiPSC differentiating, and hiPSC differentiated into proximal tubular epithelial-like cells (PTELC) to known nephrotoxins. hiPSC were differentiated into PTELC, which exhibited similar morphology to PTEC, expressed prototypical PTEC markers, and were able to undergo albumin endocytosis. When treated with two nephrotoxins, hiPSC and differentiating hiPSC were more sensitive to cisplatin than differentiated PTELC, whereas all stages were equally sensitive to cyclosporin A. Both toxins also had an inhibitory effect on albumin uptake. Our results suggest a high sensitivity of differentiating cells towards toxins, which could have an unfavorable effect on regenerative processes. To study this, our model of hiPSC differentiating into PTELC appears suitable.

Published
2023
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49. Differential Modulation of Markers of Oxidative Stress and DNA Damage in Arterial Hypertension.

Author

Kreutzmann M, Kraus BJ, Christa M, Störk S, Jansen EHJM, Stopper H, and Schupp N

Abstract

Patients with arterial hypertension have an increased risk of developing tumors, particularly renal cell carcinoma. Arterial hypertension is linked to DNA damage via the generation of oxidative stress, in which an upregulated renin-angiotensin-aldosterone system plays a crucial role. The current study investigated surrogates of oxidative stress and DNA damage in a group of hypertensive patients (HypAll, n = 64) and subgroups of well (HypWell, n = 36) and poorly (HypPoor, n = 28) controlled hypertensive patients compared to healthy controls (n = 8). In addition, a longitudinal analysis was performed with some of the hypertensive patients. Markers for oxidative stress in plasma (SHp, D-ROM, and 3-nitrotyrosine) and urine (8-oxodG, 15-F 2t -isoprostane, and malondialdehyde) and markers for DNA damage in lymphocytes (γ-H2AX and micronuclei) were measured. In HypAll, all markers of oxidative stress except malondialdehyde were increased compared to the controls. After adjustment for age, this association was maintained for the protein stress markers SHp and 3-nitrotyrosine. With regard to the markers for DNA damage, there was no difference between HypAll and the controls. Further, no significant differences became apparent in the levels of both oxidative stress and DNA damage between HypWell and HypPoor. Finally, a positive correlation between the development of blood pressure and oxidative stress was observed in the longitudinal study based on the changes in D-ROM and systolic blood pressure. In conclusion, we found increased oxidative stress in extensively treated hypertensive patients correlating with the level of blood-pressure control but no association with DNA damage.

Published
2023
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50. Nrf2 Activation Does Not Protect from Aldosterone-Induced Kidney Damage in Mice.

Author

Brinks R, Wruck CJ, Schmitz J, and Schupp N

Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2) is downregulated in chronic kidney disease (CKD). Activation of Nrf2 might be a therapeutic option in CKD. Here we investigate the effect of Nrf2 activation on aldosterone (Aldo)-induced renal injury. Wild-type (WT) mice, transgenic Keap1 hypomorphic (Nrf2ꜛ, genotype results in upregulation of Nrf2 expression) mice and WT mice treated with the Nrf2 activator sulforaphane (Sulf) received Aldo for 4 weeks. In Aldo-treated mice, kidneys were significantly heavier and pathologically altered, reflected by increased urinary albumin levels and tissue damage. In Nrf2ꜛ-Aldo mice the tubule damage marker NGAL was significantly decreased. Increased oxidative damage markers (8-OHdG, 15-isoprostane F 2t ) were measured in all Aldo-treated groups. Aldo-increased Nrf2 amounts were mainly found in the late tubule system. The amount of phosphorylated and thus putatively active Nrf2 was significantly increased by Aldo only in WT mice. However, expression of Nrf2 target genes NQO1 and HO1 was decreased in all Aldo-infused mice. GSK3β, which promotes Nrf2 degradation, was significantly increased in the kidneys of Aldo-treated WT mice. Neither genetic nor pharmacological Nrf2 activation was able to prevent oxidative injury induced by Aldo, probably due to induction of negative regulators of Nrf2.

Published
2023
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