Silencing of PPAR alpha Bb mRNA in brown trout primary hepatocytes: effects on molecular and morphological targets under the influence of an estrogen and a PPAR alpha agonist

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Madureira, TV (Author) Other; Pinheiro, I (Author) Other; Malhao, F (Author) Other; Filipe F C Castro (Author) FCUP; rocha, e (Author) ICBAS; Urbatzka, R (Author) Other

Journal

Title: COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY

Vol. 229

Pages: 1-9

ISSN: 0305-0491

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 2 Citations

Other information

Authenticus ID: P-00Q-6WA

DOI: 10.1016/j.cbpb.2018.12.001

Abstract (EN): The crosstalk between peroxisome proliferator-activated receptor alpha (PPAR alpha) and estrogenic pathways are shared from fish to humans. Salmonid fish had an additional genome duplication, and two PPAR alpha isoforms (PPARa alpha Ba and PPAR alpha Bb) were previously identified. Since a negative regulation between estrogen signaling and PPAR alpha was described, a post-transcriptional gene silencing for PPAR alpha Bb was designed in primary brown trout hepatocytes. The aims of the study were to: (i) decipher the effects of PPAR alpha Bb knock-down on peroxisome morphology and on mRNA expression of potential target genes, and (ii) to assess the cross-interferences caused by an estrogenic compound (17 alpha-ethinylestradiol - EE2) and a PPAR alpha agonist (Wy-14,643 - Wy) using the established knock-down model. A knock-down efficiency of 70% was achieved for PPAR alpha Bb and its silencing significantly reduced the volume density of peroxisomes, but did not alter mRNA levels of the studied genes. Exposure to Wy did not change peroxisome morphology or mRNA expression, but under silencing conditions Wy rescued the volume density of peroxisomes to control levels, and increased acyl-coenzyme A oxidase 1-31 (Acoxl-31) mRNA. Exposure to EE2 caused a reduction of peroxisome volume density, but under silencing conditions this effect was abolished and ApoA1 mRNA level was diminished. The morphological alterations of peroxisomes by WY and EE2 demonstrated that obtained results are PPAR alpha Bb dependent, and suggest the regulation of unknown downstream targets of PPAR alpha Bb. In summary, PPAR alpha Bb is involved in the control of peroxisome size and/or number, which opens future opportunities to explore its regulation and molecular targets.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9