Changes in ecological and environmental factors lead to an increased occurrence of cyanobacterial water blooms, while secondary metabolites-producing cyanobacteria pose a threat to both environmental and human health. Apart from oral and dermal exposure, humans may be exposed via inhalation and/or swallowing of contaminated water and aerosols. Although many studies deal with liver toxicity, less information about the effects in the respiratory system is available. We investigated the effects of a prevalent cyanotoxin, microcystin-LR (MC-LR), using respiratory system-relevant human bronchial epithelial (HBE) cells. The expression of specific organic-anion-transporting polypeptides was evaluated, and the western blot analysis revealed the formation and accumulation of MC-LR protein adducts in exposed cells. However, MC-LR up to 20 μM neither caused significant cytotoxic effects according to multiple viability endpoints after 48-h exposure, nor reduced impedance (cell layer integrity) over 96 h. Time-dependent increase of putative MC-LR adducts with protein phosphatases was not associated with activation of mitogen-activated protein kinases ERK1/2 and p38 during 48-h exposure in HBE cells. Future studies addressing human health risks associated with inhalation of toxic cyanobacteria and cyanotoxins should focus on complex environmental samples of cyanobacterial blooms and alterations of additional non-cytotoxic endpoints while adopting more advanced in vitro models.

• Klíčová slova
• 16HBE14o-, mitogen-activated protein kinase, HBE1, OATP, cytotoxicity, human bronchial epithelial cells, in vitro, microcystin-LR,
• MeSH
• bronchy cytologie   MeSH
• buněčné linie MeSH
• epitelové buňky účinky léků   metabolismus   MeSH
• extracelulárním signálem regulované MAP kinasy metabolismus   MeSH
• lidé MeSH
• mikrocystiny toxicita   MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• mořské toxiny toxicita   MeSH
• přenašeče organických aniontů genetika   MeSH
• signální transdukce účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyanoginosin LR MeSH Prohlížeč
• extracelulárním signálem regulované MAP kinasy MeSH
• mikrocystiny MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• mořské toxiny MeSH
• přenašeče organických aniontů MeSH

Toxicity and liver tumor promotion of cyanotoxins microcystins have been extensively studied. However, recent studies document that other metabolites present in the complex cyanobacterial water blooms may also have adverse health effects. In this study we used rat liver epithelial stem-like cells (WB-F344) to examine the effects of cyanobacterial extracts on two established markers of tumor promotion, inhibition of gap-junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) - ERK1/2. Extracts of cyanobacteria (laboratory cultures of Microcystis aeruginosa and Aphanizomenon flos-aquae and water blooms dominated by these species) inhibited GJIC and activated MAPKs in a dose-dependent manner (effective concentrations ranging 0.5-5mgd.w./mL). Effects were independent of the microcystin content and the strongest responses were elicited by the extracts of Aphanizomenon sp. Neither pure microcystin-LR nor cylindrospermopsin inhibited GJIC or activated MAPKs. Modulations of GJIC and MAPKs appeared to be specific to cyanobacterial extracts since extracts from green alga Chlamydomonas reinhardtii, heterotrophic bacterium Klebsiella terrigena, and isolated bacterial lipopolysaccharides had no comparable effects. Our study provides the first evidence on the existence of unknown cyanobacterial toxic metabolites that affect in vitro biomarkers of tumor promotion, i.e. inhibition of GJIC and activation of MAPKs.

• MeSH
• aktivace enzymů účinky léků   MeSH
• alkaloidy MeSH
• Aphanizomenon chemie   izolace a purifikace   MeSH
• bakteriální toxiny MeSH
• buněčné linie MeSH
• časové faktory MeSH
• extracelulárním signálem regulované MAP kinasy metabolismus   MeSH
• fosforylace účinky léků   MeSH
• karcinogeny chemie   toxicita   MeSH
• komplexní směsi chemie   toxicita   MeSH
• krysa rodu Rattus MeSH
• mezerový spoj účinky léků   MeSH
• mezibuněčná komunikace účinky léků   MeSH
• Microcystis chemie   izolace a purifikace   MeSH
• mikrocystiny analýza   toxicita   MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• sinice chemie   izolace a purifikace   MeSH
• sladká voda mikrobiologie   MeSH
• toxiny kmene Cyanobacteria MeSH
• uracil analogy a deriváty   toxicita   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• alkaloidy MeSH
• bakteriální toxiny MeSH
• cylindrospermopsin MeSH Prohlížeč
• extracelulárním signálem regulované MAP kinasy MeSH
• karcinogeny MeSH
• komplexní směsi MeSH
• mikrocystiny MeSH
• mitogenem aktivované proteinkinasy MeSH
• toxiny kmene Cyanobacteria MeSH
• uracil MeSH