title: Identification of transcriptional networks responding to pyrroloquinoline quinone dietary supplementation and their influence on thioredoxin expression, and the JAK/STAT and MAPK pathways.
abstract: PQQ (pyrroloquinoline quinone) improves energy utilization and reproductive performance when added to rodent diets devoid of PQQ. In the present paper we describe changes in gene expression patterns and transcriptional networks that respond to dietary PQQ restriction or pharmacological administration. Rats were fed diets either deficient in PQQ (PQQ-) or supplemented with PQQ (approx. 6 nmol of PQQ/g of food; PQQ+). In addition, groups of rats were either repleted by administering PQQ to PQQ- rats (1.5 mg of PQQ intraperitoneal/kg of body weight at 12 h intervals for 36 h; PQQ-/+) or partially depleted by feeding the PQQ- diet to PQQ+ rats for 48 h (PQQ+/-). RNA extracted from liver and a Codelink(R) UniSet Rat I Bioarray system were used to assess gene transcript expression. Of the approx. 10000 rat sequences and control probes analysed, 238 were altered at the P<0.01 level by feeding on the PQQ- diet for 10 weeks. Short-term PQQ depletion resulted in changes in 438 transcripts (P<0.01). PQQ repletion reversed the changes in transcript expression caused by PQQ deficiency and resulted in an alteration of 847 of the total transcripts examined (P<0.01). Genes important for cellular stress (e.g. thioredoxin), mitochondriogenesis, cell signalling [JAK (Janus kinase)/STAT (signal transducer and activator of transcription) and MAPK (mitogen-activated protein kinase) pathways] and transport were most affected. qRT-PCR (quantitative real-time PCR) and functional assays aided in validating such processes as principal targets. Collectively, the results provide a mechanistic basis for previous functional observations associated with PQQ deficiency or PQQ administered in pharmacological amounts.
authors.affiliation: Department of Nutrition, University of California Davis, 95616, USA. eskouhie@amgen.com
authors.forename: Eskouhie
authors.initials: E
authors.lastname: Tchaparian
authors.forename: Lisa
authors.initials: L
authors.lastname: Marshal
authors.forename: Gene
authors.initials: G
authors.lastname: Cutler
authors.forename: Kathryn
authors.initials: K
authors.lastname: Bauerly
authors.forename: Winyoo
authors.initials: W
authors.lastname: Chowanadisai
authors.forename: Michael
authors.initials: M
authors.lastname: Satre
authors.forename: Calliandra
authors.initials: C
authors.lastname: Harris
authors.forename: Robert B
authors.initials: RB
authors.lastname: Rucker
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000378:metabolism; D019587:Dietary Supplements; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D045542:PQQ Cofactor / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004272:DNA, Mitochondrial; D008055:Lipids; D050791:STAT Transcription Factors; D013879:Thioredoxins; D045542:PQQ Cofactor; D053612:Janus Kinases