Proteomic evidences for microcystin-RR-induced toxicological alterations in mice liver.

This study deals with the isolation and purification of an important variant of microcystins namely microcystin-RR (MCYST-RR) from Microcystis aeruginosa and reports its effects on mice liver protein profile and cellular functions. Protein profiling by 2-dimensional gel electrophoresis revealed changes in the number and accumulation of protein spots in liver of mice treated with different concentrations of MCYST-RR. Untreated (control) mice liver showed 368 protein spots while the number was 355, 348 and 332 in liver of mice treated with 200, 300 and 400 µg kg body wt of MCYST-RR respectively. Altogether 102, 97, and 92 spots were differentially up-accumulated and 93, 91, and 87 spots were down- accumulated respectively with the treatment of 200, 300, 400 µg kg body wt. Eighteen differentially accumulated proteins present in all the four conditions were identified by MALDI-TOF MS. Of these eighteen proteins, 12 appeared to be involved in apoptosis/toxicological manifestations. Pathway analysis by Reactome and PANTHER database also mapped the identified proteins to programmed cell death/apoptosis clade. That MCYST-RR induces apoptosis in liver tissues was also confirmed by DNA fragmentation assay. Results of this study elucidate the proteomic basis for the hepatotoxicity of MCYST-RR which is otherwise poorly understood till date.