Clostridium perfringens alpha-toxin-induced hemolysis of horse erythrocytes is dependent on Ca2+ uptake.
Abstract: Clostridium perfringens alpha-toxin is able to lyse various erythrocytes. Exposure of horse erythrocytes to alpha-toxin simultaneously induced hot-cold hemolysis and stimulated production of diacylglycerol and phosphorylcholine. When A23187-treated erythrocytes were treated with the toxin, these events were dependent on the concentration of extracellular Ca2+ . Incubation with the toxin of BAPTA-AM-treated horse erythrocytes caused no hemolysis or production of phosphorylcholine, but that of the BAPTA-treated erythrocytes did. When Quin 2-AM-treated erythrocytes were incubated with the toxin in the presence of 45Ca2+, the cells accumulated 45Ca2+ in a dose- and a time-dependent manner. These results suggest that the toxin-induced hemolysis and hydrolysis of phosphatidylcholine are closely related to the presence of Ca2+ in the cells. Flunarizine, a T-type Ca2+ channel blocker, and tetrandrine, an L- and T-type Ca2+ channel blocker, inhibited the toxin-induced hemolysis and Ca2+ uptake. However, L-type Ca2+ channel blockers, nifedipine, verpamil and diltiazem, an N-type blocker, omega-conotoxin SVIB, P-type blockers, omega-agatoxin TK and omega-agatoxin IVA, and a Q-type blocker, omega-conotoxin MVII C, had no such inhibitory effect. The observation suggests that Ca2+ taken up through T-type Ca2+ channels activated by the toxin plays an important role in hemolysis induced by the toxin.
Publication Date: 2003-07-02 PubMed ID: 12832089DOI: 10.1016/s0005-2736(03)00140-8Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study focuses on how the alpha-toxin of Clostridium perfringens influences the rupture of horse red blood cells and the related biochemical processes, with a key finding that these effects depend on the absorption of calcium ions in the cells.
Role of Alpha-Toxin
- The research explores the alpha-toxin from the Clostridium perfringens bacterium, responsible for damaging different types of red blood cells.
- In the case of horse red blood cells, the alpha-toxin triggers both the cells rupture (hemolysis) and stimulates the production of chemical compounds like diacylglycerol and phosphorylcholine, known for playing significant roles in cellular signalling and responses.
Importance of Calcium Ions
- The study reveals that these effects of the alpha-toxin are directly related to the concentration of calcium ions (Ca2+) in the cells which are introduced via a compound called A23187.
- Evidence is given through an experiment wherein cells were treated with BAPTA-AM, a substance that enables cells to bind with calcium ions, rendering them inactive. Results showed that both cell rupture and phosphorylcholine production were significantly reduced.
- However, when cells were incubated with alpha-toxin and a calcium ion radioisotope (45Ca2+), researchers found the cells accumulated 45Ca2+ over time. This shows that alpha-toxin promotes calcium-ion absorption in cells.
Role of Calcium Channels
- In a further exploration, researchers studied the role of calcium channels in the process of cell rupture. Specific inhibitors or “blockers” of L and T-Type calcium channels were introduced to see their effect on hemolysis.
- Flunarizine, a T-Type Ca2+ channel blocker, successfully inhibited cell rupture and calcium ion absorption.
- However, L-Type calcium channel blockers like nifedipine, verpamil, and diltiazem failed to show similar effects, implying a critical role of T-type calcium channels in this process.
Conclusion
- Ultimately, the study concludes that the entry of calcium ion through T-type calcium channels activated by the alpha-toxin of Clostridium perfringens plays a significant role in inducing hemolysis.
Cite This Article
APA
Ochi S, Oda M, Nagahama M, Sakurai J.
(2003).
Clostridium perfringens alpha-toxin-induced hemolysis of horse erythrocytes is dependent on Ca2+ uptake.
Biochim Biophys Acta, 1613(1-2), 79-86.
https://doi.org/10.1016/s0005-2736(03)00140-8 Publication
Researcher Affiliations
- Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
MeSH Terms
- Animals
- Bacterial Toxins / toxicity
- Biological Transport
- Calcium / blood
- Calcium-Binding Proteins / toxicity
- Chelating Agents / pharmacology
- Egtazic Acid / analogs & derivatives
- Egtazic Acid / pharmacology
- Erythrocytes / drug effects
- Hemolysis / drug effects
- Hemolysis / physiology
- Horses
- Kinetics
- Type C Phospholipases / toxicity
Citations
This article has been cited 13 times.- Gomaa NH, El-Aziz NKA, El-Naenaeey EY, Abdelaziz WS, Sewid AH. Antimicrobial potential of myricetin-coated zinc oxide nanocomposite against drug-resistant Clostridium perfringens.. BMC Microbiol 2023 Mar 22;23(1):79.
- Wang XY, Cai DZ, Li X, Bai SF, Yan FM. Identification and Physicochemical Properties of the Novel Hemolysin(s) From Oral Secretions of Helicoverpa armigera (Lepidoptera: Noctuidae).. J Insect Sci 2021 Nov 1;21(6).
- Monturiol-Gross L, Villalta-Romero F, Flores-Díaz M, Alape-Girón A. Bacterial phospholipases C with dual activity: phosphatidylcholinesterase and sphingomyelinase.. FEBS Open Bio 2021 Dec;11(12):3262-3275.
- Mehdizadeh Gohari I, A Navarro M, Li J, Shrestha A, Uzal F, A McClane B. Pathogenicity and virulence of Clostridium perfringens.. Virulence 2021 Dec;12(1):723-753.
- Nagahama M, Seike S, Ochi S, Kobayashi K, Takehara M. Clostridium perfringens Epsilon-Toxin Impairs the Barrier Function in MDCK Cell Monolayers in a Ca(2+)-Dependent Manner.. Toxins (Basel) 2020 Apr 30;12(5).
- Xu C, She Y, Fu F, Lin Y, Xu C. Study of the Structure and Biological Activity of the Amino-Terminus of the α-Toxin from Clostridium welchii Type A.. Curr Microbiol 2019 Oct;76(10):1175-1185.
- Uojima H, Onoue M, Hidaka H, Wada N, Tanaka Y, Inoue T, Kubota K, Nakazawa T, Shibuya A, Koizumi W. A suspected case of Clostridium perfringens sepsis with intravascular hemolysis after transhepatic arterial chemoembolization: a case report.. J Med Case Rep 2019 Apr 27;13(1):125.
- Navarro MA, McClane BA, Uzal FA. Mechanisms of Action and Cell Death Associated with Clostridium perfringens Toxins.. Toxins (Basel) 2018 May 22;10(5).
- Takagishi T, Takehara M, Seike S, Miyamoto K, Kobayashi K, Nagahama M. Clostridium perfringens α-toxin impairs erythropoiesis by inhibition of erythroid differentiation.. Sci Rep 2017 Jul 12;7(1):5217.
- Ali Nasir A, Younus M, Rashid A, Abdul Khaliq S, Khan E, Shah SH, Aslam A, Ghumman MA, Joiya MH. Clinico-pathological findings of Clostridium perfringens type D enterotoxaemia in goats and its hemolytic activity in different erythrocytes.. Iran J Vet Res 2015 Winter;16(1):94-9.
- Kurasawa M, Nishikido T, Koike J, Tominaga S, Tamemoto H. Gas-forming liver abscess associated with rapid hemolysis in a diabetic patient.. World J Diabetes 2014 Apr 15;5(2):224-9.
- Montes LR, López DJ, Sot J, Bagatolli LA, Stonehouse MJ, Vasil ML, Wu BX, Hannun YA, Goñi FM, Alonso A. Ceramide-enriched membrane domains in red blood cells and the mechanism of sphingomyelinase-induced hot-cold hemolysis.. Biochemistry 2008 Oct 28;47(43):11222-30.
- Bai JN, Zhang Y, Zhao BH. Cloning of alpha-beta fusion gene from Clostridium perfringens and its expression.. World J Gastroenterol 2006 Feb 28;12(8):1229-34.
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