Icariin attenuate microcystin-LR-induced gap junction injury in Sertoli cells through suppression of Akt pathways

Environ Pollut. 2019 Aug:251:328-337. doi: 10.1016/j.envpol.2019.04.114. Epub 2019 Apr 26.

Abstract

Microcystin-leucine-arginine (MC-LR) can cause male reproductive disorder. However, the underlying mechanism are not yet entirely elucidated. In this study, we aimed to investigated the effects of MC-LR on the integrity of blood-testis barrier (BTB) and the related molecular mechanisms. Both in vivo and in vitro experiments revealed that MC-LR caused disruption of BTB and gap junctions between Sertoli cells respectively, which was paralleled by the alteration of connexin43 (Cx43). Our data demonstrated that MC-LR decreased gap junction intercellular communication (GJIC) and impaired Cx43 expression by activating the phosphatidylinositol 3-kinase/Akt cascades. In addition, a possible protective effect of Icariin (ICA), a flavonoid isolated from Chinese medicinal herb, against MC-LR toxicity was investigated. The ICA prevented the degradation of GJIC and impairment of Cx43 induced by MC-LR via suppressing the Akt pathway. Together, our results confirmed that the expression of Cx43 induced by MC-LR was regulated in vivo and in vitro, which was involved in the destruction of BTB. Additionally, ICA seems to be able to mitigate the MC-LR toxic effects.

Keywords: Akt; Connexin43; Gap junctions; Icariin; Microcystin-LR.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Connexin 43 / metabolism
  • Drugs, Chinese Herbal / pharmacology*
  • Flavonoids / pharmacology*
  • Gap Junctions / drug effects*
  • Gap Junctions / metabolism
  • Male
  • Marine Toxins
  • Mice
  • Microcystins / toxicity*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Sertoli Cells / drug effects*
  • Sertoli Cells / metabolism
  • Signal Transduction / drug effects

Substances

  • Connexin 43
  • Drugs, Chinese Herbal
  • Flavonoids
  • GJA1 protein, mouse
  • Marine Toxins
  • Microcystins
  • Proto-Oncogene Proteins c-akt
  • cyanoginosin LR
  • icariin