High concentrations of L-lysine cause mitochondrial damage and necrosis in isolated pancreatic acinar cells

Sep 30, 2026

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Investigation focuses on how high concentrations of basic amino acids, especially L-lysine (L-Lys), affect isolated pancreatic acinar cells, aiming to clarify mitochondrial involvement in acute pancreatitis mechanisms. Isolated mouse or rat acinar cells were exposed to 10–60 mM L-Lys, L-arginine (L-Arg) or L-ornithine (L-Orn). Electron microscopy assessed mitochondrial morphology, while mitochondrial membrane potential (ΔΨm) and ATP levels evaluated mitochondrial function, alongside Ca2+ dynamics, trypsin activity, and cell viability. L-Lys induced mitochondrial swelling, reduced ΔΨm and ATP, did not alter intracellular Ca2+ or early trypsinogen activation, and primarily triggered necrosis.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Background

Acute pancreatitis and known mechanisms

Experimental models using basic amino acids

Study aim

Materials and methods

Materials and solutions

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN High concentrations of L-lysine cause mitochondrial damage and necrosis in isolated pancreatic acinar cells EszterT. Végh1,2,3, Zsolt Balla1, Ágnes Dágó1, Ola Salamah1, BrigittaTóth1, Jason Elperin2,3, Steven Speakman2,3, Natalia Shalbueva2,3, Petra Pallagi4, Zsolt Rázga5,6, Lóránd Kiss1, Anna Gukovskaya2,3 & Zoltán Rakonczay Jr.1􀀍 Intraperitoneal administration of high doses of basic amino acids, such as L-lysine (L-Lys), L-arginine (L-Arg) or L-ornithine (L-Orn) induces acute pancreatitis in rodents. Although the exact mechanism of their action is not fully understood, the role of mitochondria has been implicated. We aimed to investigate the effects of basic amino acids, particularly L-Lys, on isolated pancreatic acinar cells. Isolated mouse or rat pancreatic acinar cells were treated with high concentrations (10–60 mM) of L-Lys, L-Arg or L-Orn. The morphology of acinar mitochondria was observed by electron microscopy. The function of mitochondria was assessed by mitochondrial membrane potential (∆Ψm) and cellular ATP level measurements. Changes in intracellular Ca2+ concentration ([Ca2+ ]i), trypsin activity and cellular viabilities were also determined. Treatment of acinar cells with L-Lys caused mitochondrial swelling. L-Lys and L-Arg markedly decreased ∆Ψm after 6 h of treatment, whereas L-Orn had a less pronounced effect than L-Lys or L-Arg. Intracellular ATP levels were also reduced by basic amino acids. L-Lys did not alter [Ca2+ ]i and did not induce early trypsinogen activation. Furthermore, L-Lys administration primarily caused acinar necrosis. Overall, L-Lys primarily damaged pancreatic acinar mitochondria and caused necrotic cell death without affecting the initial [Ca2+ ]i. Keywords Acute pancreatitis, L-lysine, L-arginine, L-ornithine, Basic amino acids, Pancreatic acinar cells Abbreviations ∆Ψm Mitochondrial membrane potential AP Acute pancreatitis ANOVA Analysis of variance BAPTA-AM 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis (acetoxymethyl ester)[Ca2+]i Intracellular Ca2+ concentration FCCP Carbonyl cyanide p-trifluoromethoxy-phenylhydrazone L-Arg L-arginine L-Lys L-lysine L-Orn L-ornithine NF-κB Nuclear factor-κB OsO Osmium tetroxide 4 PBS Phosphate-buffered saline PI Propidium iodide RIPA Radioimmunoprecipitation assay TMRM Tetramethylrhodamine methyl ester 1Department of Pathophysiology, University of Szeged, P.O. Box: 427, Szeged 6701, Hungary. 2David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. 3VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA. 4Department of Medicine, University of Szeged, Szeged, Hungary. 5Department of Pathology, University of Szeged, Szeged, Hungary. 6Zsolt Rázga is deceased. 􀀍 email: [rakonczay.zoltan@med.u-szeged.hu](rakonczay.zoltan@med.u-szeged.hu) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) Acute pancreatitis (AP) is an inflammatory disorder of the pancreas1. The principal etiological factors of the disease are alcohol consumption, bile stone-induced obstruction, hypertriglyceridaemia and endoscopic cholangiopancreatography2. AP severity is classified as mild, moderate or severe3. The mortality rate of AP is high, particularly in its severe form4, and there is no specific treatment5. Despite intensive research on this disorder, the pathomechanism of AP is not fully understood, but it includes early intracellular Ca2+ overload, loss of mitochondrial membrane potential (∆Ψm) with mitochondrial damage, premature digestive enzyme activation, nuclear factor-κB (NF-κB) signaling, release of inflammatory cytokines and leukocyte infiltration6,7. To investigate the pathomechanisms during AP, animal models are typically used. There are several experimental models8, each of which has different advantages and disadvantages9, 10. Intraperitoneal administrati

FAQs

What is the study’s primary focus regarding L-lysine (L-Lys)?

The study examines how high concentrations of L-Lys affect isolated rodent pancreatic acinar cells, including Ca2+ responses, early trypsinogen activation, mitochondrial morphology and function, and cell death modes.

How were mitochondrial damage and function evaluated in treated acinar cells?

Mitochondrial morphology was observed by electron microscopy, and mitochondrial function was assessed using mitochondrial membrane potential (ΔΨm) and cellular ATP level measurements.

Does L-Lys trigger early trypsinogen activation or intracellular Ca2+ overload in this model?

L-Lys did not alter intracellular Ca2+ concentration and did not induce early trypsinogen activation, despite causing mitochondrial injury and necrotic cell death.

Sep 30, 2026

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