Autoinducer N-(3-oxododecanoyl)-l-homoserine lactone induces calcium and reactive oxygen species-mediated mitochondrial damage and apoptosis in blood platelets. (May 2021)

• Record Type: Journal Article
• Authors: Yadav, Vivek Kumar; Singh, Pradeep Kumar; Sharma, Deepmala; Pandey, Himanshu; Singh, Sunil Kumar; Agarwal, Vishnu
• Is Part Of: Microbial pathogenesis. Volume 154(2021)
• Publication Date: 2021-05
• Subjects: Platelet -- Apoptosis -- Acyl-homoserine lactones -- Pseudomonas aeruginosa; AHL Acyl-homoserine lactone -- 3-oxo-C12HSL N-3-oxo-dodecanoyl-l-homoserine lactone -- C4 HSL N-butyryl-l-homoserine lactone -- ROS Reactive oxygen species -- MTT 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide -- PS phosphatidylserine -- mPTP Mitochondrial permeability transition pore -- DPI Diphenyleneiodonium chloride -- QS Quorum Sensing -- CCCP Carbonyl cyanide 3-chlorophenylhydrazone -- JC-1 5, 5V, 6, 6V-tetrachloro-1, 1V3, 3V-tetra ethyl benzimidazol carbocyanine iodide -- BAPTA 1, 2-bis(o-aminophenoxy)ethane-N, N, N′, N'-tetraacetic acid -- EGTA Ethylene glycol-bis(β-aminoethyl ether)-N, N, N′, N'-tetraacetic acid; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2021.104792
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: Acylated homoserine lactones (AHL) such as N-(3-oxododecanoyl)-l -homoserine lactone (3-oxo-C12 HSL) and N-butyryl-l -homoserine lactone (C4 HSL) are the most common autoinducer molecules in Pseudomonas aeruginosa . These AHL molecules not only regulate the expression of virulence factors but also have been shown to interfere with the host cell and modulate its functions. Recently, we reported that 3-oxo-C12 HSL but not C4 HSL causes cytosolic Ca 2+ rise and ROS production in platelets. In this study, we examined the potential of AHLs to induce apoptosis in the human blood platelet. Our result showed that 3-oxo-C12 HSL but not C4 HSL causes phosphatidylserine (PS) exposure, mitochondrial dysfunction (mitochondrial transmembrane potential loss, and mitochondrial permeability transition pore (mPTP) formation). Besides, 3-oxo-C12 HSL also inhibited thrombin-induced platelet aggregation and clot retraction. The pretreatment of an intracellular calcium chelator BAPTA-AM or ROS inhibitor (DPI) significantly attenuated the 3-oxo-C12 HSL induced apoptotic characters such as PS exposure and mitochondrial dysfunctions. These data, including our previous findings, confirmed that 3-oxo-C12 HSL induced intracellular Ca 2+ mediated ROS production results in the activation and subsequent induction of apoptotic features in platelets. Our results demonstrated that the 3-oxo-C12 HSL modulates the functions of platelets that may cause severe thrombotic complications in P. aeruginosa infected individuals. Highlights: Pseudomonas aeruginosa associated quorum sensing molecule 3-oxo-C12 HSL but not C4 HSL induces apoptosis in blood platelets. 3-oxo-C12 HSL inhibits the thrombin-induced platelet aggregation and clot retraction. Intracellular Ca 2+ and ROS play an important role in 3-oxo-C12 HSL induced platelet apoptosis.