Sex-specific differences in redox signalling pathways in diabetes

Diabetes is a metabolic disease characterized by defects in insulin secretion or action, leading to chronic hyperglycemia that affect different organs. The global prevalence of diabetes in men is higher than in women, which is to date mainly explained by differences in hormones or epigenetic modifications. While the cause of diabetes is predominantly either genetic or due to an unhealthy lifestyle, oxidative stress has been reported as an important factor in the pathophysiology. Research about gender influence on pathological mechanisms of ROS in the development and progression of diabetes is recently evolving. However, only little is known about distinct molecular mechanisms which could be highly significant for the development of gender-specific therapies. To address this question, the goal of the study is to analyze gender-dependent molecular (redox) changes in a broad range of tissues.

More specifically, using a combination of genetic and chemical tools, animal and cellular models, we aim to investigate in male and female mice:

  1. Redox components composition, distribution and expression
  2. activation and resistance to oxidative stress
  3. redox proteomics
  4. cellular/molecular mechanisms by which different sex hormones modulate the above mentioned pathways.

In summary, we aim to reveal novel gender-specific molecular redox profiles in the pathophysiology of diabetes with information on subcellular production sites. Investigation of differentially expressed genes and the extent and location of oxidative modifications in the proteome could facilitate a better understanding for the prevention and treatment of diabetes.

Portraitfoto von Prof. Dr. rer. nat. Leticia Prates Roma

Project lead

Prof. Leticia Prates Roma

University of Saarland
Medical Faculty, ZHMB, CIPMM
Dept. Biophysics

leticia.prates-roma(at)uks.eu
ORCiD: 0000-0001-9527-0529

Curriculum Vitae

 

 
Portraitfot von Dr. Janina Frisch

Dr. rer. nat. Janina Frisch

University of Saarland
Medical Faculty, ZHMB, CIPMM
Dept. Biophysics

janina.frisch(at)uks.eu
ORCiD: 0009-0003-9344-1728

Curriculum Vitae

 

 

Important publications

1) Wollenhaupt J, Frisch J§, Harlacher E, Wong DWL, Jin H, Schulte C, Vondenhoff S, Moellmann J, Klinkhammer BM, Zhang L, Baleanu-Curaj A, Liehn EA, Speer T, Kazakov A, Werner C, van der Vorst EPC, Selejan SR, Hohl M, Böhm M, Kramann R, Biessen EAL, Lehrke M, Marx N, Jankowski J, Maack C, Boor P, Prates Roma L*, Noels H*. Pro-oxidative priming but maintained cardiac function in a broad spectrum of murine models of chronic kidney disease.Redox Biol. 2022 Oct;56:102459. doi: 10.1016/j.redox.2022.102459. Epub 2022 Aug 30. (IF: 10.8) §shared first-author; *shared corresponding author

2)Wrublewsky S, Glas J, Carlein C, Nalbach L, Hoffmann MDA, Pack M, Vilas-Boas EA, Ribot N, Kappl R, Menger MD, Laschke MW, Ampofo E*, Roma LP*. The loss of pancreatic islet NADPH oxidase (NOX)2 improves islet transplantation. Redox Biol. 2022 Jul 31;55:102419. doi: 10.1016/j.redox.2022.102419. (IF: 10.8) * shared last authorship

3) Bertero E, Nickel A, Kohlhaas M, Hohl M, Sequeira V, Brune C, Schwemmlein J, Abeßer M, Schuh K, Kutschka I, Carlein C, Münker K, Atighetchi S, Müller A, Kazakov A, Kappl R, von der Malsburg K, van der Laan M, Schiuma AF, Böhm M, Laufs U, Hoth M, Rehling P, Kuhn M, Dudek J, von der Malsburg A, Prates Roma L, Maack C (2021). Loss of Mitochondrial Ca2+ Uniporter Limits Inotropic Reserve and Provides Trigger and Substrate for Arrhythmias in Barth Syndrome Cardiomyopathy. Circulation. Nov 23;144(21):1694-1713. doi: 10.1161/CIRCULATIONAHA.121.053755. Epub 2021 Oct 14. (IF 39.92)

4) Schunk SJ, Triem S, Schmit D, Zewinger S, Sarakpi T, Becker E, Hütter G, Wrublewsky S, Küting F, Hohl M, Alansary D, Prates Roma L, Lipp P, Möllmann J, Lehrke M, Laschke MW, Menger MD, Kramann R, Boor P, Jahnen-Dechent W, März W, Böhm M, Laufs U, Niemeyer BA, Fliser D, Ampofo E, Speer T (2021). Interleukin-1α Is a Central Regulator of Leukocyte-Endothelial Adhesion in Myocardial Infarction and in Chronic Kidney Disease. Circulation. Sep 14;144(11):893-908. doi: 10.1161/CIRCULATIONAHA.121.053547. (IF 39.92)

5) Vilas-Boas E,Nalbach L, Ampofo E, Lucena CF, Ortis F, Carpinelli AR, Morgan B, Roma LP (2021). Transient NADPH oxidase 2-dependent H2O2 production drives early palmitate-induced lipotoxicity in pancreatic islets. Free Radic Biol Med. Jan; 162:1-13. doi: 10.1016/j.freeradbiomed.2020.11.023 (IF: 8.01)

6) Soppert J*, Frisch J*, Wirth J, Hemmers C, Boor P, Kramann R, Vondenhoff S, Moellmann J, Lehrke M, Hohl M, van der Vorst E, Werner C, Speer T, Maack C, Marx N, Jankowski J, Roma LP, Noels H (2022). A systematic review and meta-analysis of murine models of uremic cardiomyopathy. Kidney Int 2022 Feb;101(2):256-273. doi: 10.1016/j.kint.2021.10.025. Epub 2021 Nov 11 (IF 18.9)* shared first authorship

7) Junho CVC, Frisch J, Soppert J, Wollenhaupt J, Noels H (2023). Cardiomyopathy in chronic kidney disease: clinical features, biomarkers and the contribution of murine models in understanding pathophysiology. Clin KidneyJ 2023 Apr 18;16(11):1786-1803. doi: 10.1093/ckj/sfad085. eCollection 2023 Nov (IF 4.6)

8) Reul J*, Frisch J*, Engeland CE, Thalheimer FB, Hartmann J, Ungerechts G, Buchholz CJ (2019). Tumor-Specific Delivery of Immune Checkpoint Inhibitors by Engineered AAV Vectors. Front Oncol 2019 Feb 14:9:52. doi: 10.3389/fonc.2019.00052. eCollection 2019 (IF 6.2) * shared first authorship