Cylindrospermopsin impairs vascular smooth muscle cells by P53-mediated apoptosis due to ROS overproduction

Toxicol Lett. 2021 Dec 15:353:83-92. doi: 10.1016/j.toxlet.2021.10.006. Epub 2021 Oct 20.

Abstract

Cylindrospermopsin (CYN) is a toxic secondary metabolite from cyanobacteria that can cause cardiovascular disease. However, the study of CYN-induced cardiovascular toxicity in vitro is very limited and the mechanism is remain to be clarified. Vascular smooth muscle cells (VMSCs) have an important function in maintaining the structural and functional integrity of the aortic wall, and are an important in vitro model for cardiovascular research. Thus, the effects of CYN exposure (2, 20, 200, and 2000 nM) on VMSCs were analyzed. In vitro study, results showed that CYN exposure decreased VMSCs viability, inhibited VMSCs migration, induced DNA damage, destroyed cytoskeleton, changed cell morphology, promoted VMSCs apoptosis, and increased intracellular reactive oxygen species (ROS) levels. In addition, CYN could induce the activities of SOD, CAT and GPX, and promote the expressions of SOD1, CAT, GPx1, p53 and Bax genes and inhibit the expression of Bcl-2 gene, leading to a higher ratio of Bax/Bcl-2. Taken together, CYN may induce ROS overproduction, leading to increased p53 expression and ultimately promoting VSMC apoptosis. Therefore, the present study demonstrates that CYN could impair VMSCs, leading to vascular developmental defects and angiocardiopathy.

Keywords: Apoptosis; Cylindrospermopsin; Reactive oxygen species; Vascular smooth muscle cell; p53.

MeSH terms

  • Alkaloids / administration & dosage
  • Alkaloids / toxicity*
  • Animals
  • Catalase / genetics
  • Catalase / metabolism
  • Cell Line
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cyanobacteria Toxins / administration & dosage
  • Cyanobacteria Toxins / toxicity*
  • DNA Damage
  • Gene Expression Regulation, Enzymologic
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Muscle, Smooth, Vascular / drug effects*
  • Rats
  • Reactive Oxygen Species
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Alkaloids
  • Cyanobacteria Toxins
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • cylindrospermopsin
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase