Dataset Information

Cyclophilin A is not acetylated at Lysine-82 and Lysine-125 in resting and stimulated platelets

ABSTRACT: Cyclophilin A (CyPA), a member of the family of cyclophilins, is widely expressed by all prokaryotic and eukaryotic cells. Upon activation, CyPA can also be released from platelets, and engages in extracellular functions via interaction with the CD147 receptor that contribute to cardiovascular disease. CyPA was recently found to be acetylated at K82 and K125, two lysines conserved in most species, and these modifications were required for secretion of acetylated CyPA in response to cell activation in vascular smooth muscle cells. We here addressed whether acetylation at these sitesis also required for release of acetylated CyPA from platelets. Western blot analyses demonstrated the presence of CyPA in human and mouse platelets. Thrombin-stimulation resulted in CyPA release from platelets, however, no acetylation was observed –neither in cell lysates nor in supernatants of untreatedand thrombin-activated platelets. Similar results were obtained after immunoprecipitation of CyPA from platelets. In vitro acetylation of recombinant humanCyPA by p300 acetyltransferase likewise did not induce CyPA acetylation. Using shotgun proteomics we detected two CyPA peptide precursors in the recombinant protein, acetylatedat K28, but again no acetylation was found in CyPA from resting or stimulated platelet samples. Our findings suggest that acetylation of CyPA is not a major protein modification in platelets, and that CyPA acetylation at K82 and K125 is not required for its secretion from platelets.

INSTRUMENT(S): LTQ Orbitrap Velos, Q Exactive HF

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Blood Platelet

SUBMITTER: Stefan Loroch

LAB HEAD: Albert Sickmann

PROVIDER: PXD027289 | Pride | 2022-02-22

REPOSITORIES: Pride

ACCESS DATA

Publications

Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets.

Rosa Annabelle A Butt Elke E Hopper Christopher P CP Loroch Stefan S Bender Markus M Schulze Harald H Sickmann Albert A Vorlova Sandra S Seizer Peter P Heinzmann David D Zernecke Alma A

International journal of molecular sciences 20220127 3

Cyclophilin A (CyPA) is widely expressed by all prokaryotic and eukaryotic cells. Upon activation, CyPA can be released into the extracellular space to engage in a variety of functions, such as interaction with the CD147 receptor, that contribute to the pathogenesis of cardiovascular diseases. CyPA was recently found to undergo acetylation at K82 and K125, two lysine residues conserved in most species, and these modifications are required for secretion of CyPA in response to cell activation in v ...[more]

PMID: 35163387

Similar Datasets

Project description:Heart Failure with preserved Ejection Fraction (HFpEF) is a major global health problem but there are no effective therapies. The aim of this study was to assess the effects of histone deacetylase (HDAC) inhibition on cardiopulmonary structure, function, and metabolism in a large mammalian (feline) pressure overload model with HFpEF features. Male domestic short hair cats (n=26, aged 2mo), underwent either a sham procedure (n=5) or aortic constriction (n=21) using a pre-shaped band, resulting in slow-progressive pressure overload during subsequent growth. Two-months post-banding, banded cats were treated daily with either 10mg/kg suberoylanilide hydroxamic acid (b+SAHA) (n=8), an FDA approved pan-HDAC inhibitor, or vehicle (b+veh) (n=8) for 2 months. Echocardiography at 4-months post-banding revealed that b+SAHA animals had a significant reduction in left ventricular hypertrophy (LVH) and LA size vs b+veh animals. Invasively measured left ventricular end-diastolic pressure (LVEDP) and mean pulmonary arterial pressure (mPAP) were significantly elevated in b+veh and significantly reduced by b+SAHA. SAHA speeded ex-vivo myofibril relaxation independent of LVH and this effect correlated with in-vivo indices of LV relaxation. Furthermore, SAHA preserved lung structure, improved lung compliance and oxygenation, reflected by a decrease in alveolar-capillary wall thickness, alveolar-arterial oxygen gradient (A-aDO2), and intrapulmonary shunt. SAHA also reduced perivascular fluid cuffs around extra-alveolar vessels, suggesting attenuated alveolar-capillary stress failure. Acetylation proteomics revealed that SAHA altered protein acetylation in cat hearts, including histones, many mitochondrial metabolic enzymes involved in electron transport chain, TCA cycle, malate aspartate shuttle and beta oxidation, as well as cytoskeletal proteins important for muscle function. These results suggest that acetylation defects in hypertrophic stress states can be reversed by HDAC inhibitors and may be useful to improve cardiac structure and function in HFpEF patients.

Dataset Information

Cyclophilin A is not acetylated at Lysine-82 and Lysine-125 in resting and stimulated platelets

Publications

Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure