Evidence for fumonisin inhibition of ceramide synthase in humans consuming maize-based foods and living in high exposure communities in Guatemala.
METHODS
Fumonisin (FB) occurs in maize and is an inhibitor of ceramide synthase (CerS). We determined the urinary FB1 (UFB1 ) and sphingoid base 1-phosphate levels in blood from women consuming maize in high and low FB exposure communities in Guatemala.


RESULTS
FB1 intake was estimated using the UFB1 . Sphinganine 1-phosphate (Sa 1-P), sphingosine 1-phosphate (So 1-P), and the Sa 1-P/So 1-P ratio were determined in blood spots collected on absorbent paper at the same time as urine collection. In the first study, blood spots and urine were collected every 3 months (March 2011 to February 2012) from women living in low (Chimaltenango and Escuintla) and high (Jutiapa) FB exposure communities (1240 total recruits). The UFB1 , Sa 1-P/So 1-P ratio, and Sa 1-P/mL in blood spots were significantly higher in the high FB1 intake community compared to the low FB1 intake communities. The results were confirmed in a follow-up study (February 2013) involving 299 women living in low (Sacatepéquez) and high (Santa Rosa and Chiquimula) FB exposure communities.


CONCLUSIONS
High levels of FB1 intake are correlated with changes in Sa 1-P and the Sa 1-P/So 1-P ratio in human blood in a manner consistent with FB1 inhibition of CerS.
Toxicology and Mycotoxin Research Unit, US National Poultry Research Center, USDA - ARS, R.B. Russell Research Center, Athens, GA, USA.
Ronald T
RT
Riley
Laboratorio Diagnostico Molecular S.A, Guatemala City, Guatemala.|Centro de Investigaciones en Nutrición y Salud, Guatemala City, Guatemala.
Olga
O
Torres
Centro de Investigaciones en Nutrición y Salud, Guatemala City, Guatemala.
Jorge
J
Matute
Department of Medicine, Duke University Medical Center, Durham, NC, USA.
Simon G
SG
Gregory
Department of Medicine, Duke University Medical Center, Durham, NC, USA.
Allison E
AE
Ashley-Koch
Toxicology and Mycotoxin Research Unit, US National Poultry Research Center, USDA - ARS, R.B. Russell Research Center, Athens, GA, USA.
Jency L
JL
Showker
Toxicology and Mycotoxin Research Unit, US National Poultry Research Center, USDA - ARS, R.B. Russell Research Center, Athens, GA, USA.
Trevor
T
Mitchell
Toxicology and Mycotoxin Research Unit, US National Poultry Research Center, USDA - ARS, R.B. Russell Research Center, Athens, GA, USA.
Kenneth A
KA
Voss
Department of Pharmacology, School of Medicine, Creighton University, Omaha, NE, USA.
Joyce R
JR
Maddox
Department of Pharmacology, School of Medicine, Creighton University, Omaha, NE, USA.
Janee B
JB
Gelineau-van Waes
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D037341:Fumonisins / Q000633:toxicity* / Q000652:urine; D006801:Humans; D008246:Lysophospholipids / Q000097:blood; D008875:Middle Aged; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000097:blood; D003313:Zea mays / Q000382:microbiology*
D015415:Biomarkers; D004791:Enzyme Inhibitors; D037341:Fumonisins; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; C056933:fumonisin B1; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; D013110:Sphingosine
Ceramide synthase; Fumonisin; Maize; Sphinganine 1-phosphate; Urinary fumonisin