INHIBITION OF PROTEIN SERINE/THREONINE PHOSPHATASES BY FUMONISIN B1, A MYCOTOXIN

Authors: FUKUDA, HIROKAZU - NCCRI, TOKYO, JAPAN; SHIMA, HIROSHI - NCCRI, TOKYO, JAPAN; Vesonder, Ronald; TOKUDA, HARUKUNI - KYOTO PREF UNIV, JAPAN; NISHINO, HOYOKU - KYOTO PREF UNIV, JAPAN; KATOH, SEISHI - SCRC, KANAGAWA, JAPAN; TAMURA, SHINRI - TOHOKU UNIV, MIYAGI/JAPAN; SUGIMURA, TAKASHI - NCCRI, TOKYO, JAPAN; NAGAO, MINAKO - NCCRI, TOKYO, JAPAN

Submitted to: Biochemical and Biophysical Research Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/9/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: The toxin called fumonisin is found in corn, a human and animal food staple in the USA. Fumonisin is a promotor of tumors. The mechanism for fumonisin promotion of tumors is not known. This study of fumonisin showed that it inhibited a group of enzymes involved in maintaining the stability of cells so that they do not become cancerous. This formation will be useful for scientists working in cell biology and studying the mechanism of tumor onset.

Technical Abstract: Fumonisin B1 (FB1), a mycotoxin produced by the fungus Fusarium moniliforme, which is a common contaminant of corn, is suspected to be a cause of human esophageal cancer. FB1 is hepatotoxic and hepatocarcinogenic in rats, and although the mechanisms involved have not been clarified, the latter is associated with a weak initiating activity. The effects of FB1 on the activity of protein serine/threonine phosphatases (PPs) (PP1, PP2A, PP2B, PP2C and PP5/T/K/H) were investigated in the present study. Inhibition of dephosphorylation was noted for all five PPs with IC50 values of 80 uM-3000 uM. Among the five PPs examined, PP5 was most sensitive with an IC50 of 80 uM. This concentration is comparable to that estimated to be reached in the rat body by feeding FB1 to obtain hepatic tumors. Inhibition of PP5 could thus play important roles in the toxicity and carcinogenic action of FB1.