Pushpa Rampratap

All Publications

• Resolving Atomic-Level Dynamics and Interactions of High-Molecular-Weight Hyaluronic Acid by Multidimensional Solid-State NMR ACS APPLIED MATERIALS & INTERFACES Rampratap, P., Lasorsa, A., Arunachalam, A., Kamperman, M., Walvoort, M. C., van der Wel, P. A. 2024; 16 (33): 43317-43328

  View details for DOI 10.1021/acsami.4c08428

  View details for Web of Science ID 001289142200001

• Anomalous peroxidase activity of cytochrome c is the primary pathogenic target in Barth syndrome NATURE METABOLISM Kagan, V. E., Tyurina, Y. Y., Mikulska-Ruminska, K., Damschroder, D., Vieira Neto, E., Lasorsa, A., Kapralov, A. A., Tyurin, V. A., Amoscato, A. A., Samovich, S. N., Souryavong, A. B., Dar, H. H., Ramim, A., Liang, Z., Lazcano, P., Ji, J., Schmidtke, M. W., Kiselyov, K., Korkmaz, A., Vladimirov, G. K., Artyukhova, M. A., Rampratap, P., Cole, L. K., Niyatie, A., Baker, E., Peterson, J., Hatch, G. M., Atkinson, J., Vockley, J., Kuehn, B., Wessells, R., van der Wel, P. A., Bahar, I., Bayir, H., Greenberg, M. L. 2023; 5 (12): 2184-+

  Abstract

  Barth syndrome (BTHS) is a life-threatening genetic disorder with unknown pathogenicity caused by mutations in TAFAZZIN (TAZ) that affect remodeling of mitochondrial cardiolipin (CL). TAZ deficiency leads to accumulation of mono-lyso-CL (MLCL), which forms a peroxidase complex with cytochrome c (cyt c) capable of oxidizing polyunsaturated fatty acid-containing lipids. We hypothesized that accumulation of MLCL facilitates formation of anomalous MLCL-cyt c peroxidase complexes and peroxidation of polyunsaturated fatty acid phospholipids as the primary BTHS pathogenic mechanism. Using genetic, biochemical/biophysical, redox lipidomic and computational approaches, we reveal mechanisms of peroxidase-competent MLCL-cyt c complexation and increased phospholipid peroxidation in different TAZ-deficient cells and animal models and in pre-transplant biopsies from hearts of patients with BTHS. A specific mitochondria-targeted anti-peroxidase agent inhibited MLCL-cyt c peroxidase activity, prevented phospholipid peroxidation, improved mitochondrial respiration of TAZ-deficient C2C12 myoblasts and restored exercise endurance in a BTHS Drosophila model. Targeting MLCL-cyt c peroxidase offers therapeutic approaches to BTHS treatment.

  View details for DOI 10.1038/s42255-023-00926-4

  View details for Web of Science ID 001107015000002

  View details for PubMedID 37996701

  View details for PubMedCentralID PMC11213643

• Production of isotopically enriched high molecular weight hyaluronic acid and characterization by solid-state NMR CARBOHYDRATE POLYMERS Rampratap, P., Lasorsa, A., Perrone, B., van der Wel, P. A., Walvoort, M. C. 2023; 316: 121063

  Abstract

  Hyaluronic acid (HA) is a naturally occurring polysaccharide that is abundant in the extracellular matrix (ECM) of all vertebrate cells. HA-based hydrogels have attracted great interest for biomedical applications due to their high viscoelasticity and biocompatibility. In both ECM and hydrogel applications, high molecular weight (HMW)-HA can absorb a large amount of water to yield matrices with a high level of structural integrity. To understand the molecular underpinnings of structural and functional properties of HA-containing hydrogels, few techniques are available. Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for such studies, e.g. 13C NMR measurements can reveal the structural and dynamical features of (HMW) HA. However, a major obstacle to 13C NMR is the low natural abundance of 13C, necessitating the generation of HMW-HA that is enriched with 13C isotopes. Here we present a convenient method to obtain 13C- and 15N-enriched HMW-HA in good yield from Streptococcus equi subsp. zooepidemicus. The labeled HMW-HA has been characterized by solution and magic angle spinning (MAS) solid-state NMR spectroscopy, as well as other methods. These results will open new ways to study the structure and dynamics of HMW-HA-based hydrogels, and interactions of HMW-HA with proteins and other ECM components, using advanced NMR techniques.

  View details for DOI 10.1016/j.carbpol.2023.121063

  View details for Web of Science ID 001019328700001

  View details for PubMedID 37321744