Poly(ADP) ribose polymerase-1 ablation alters eicosanoid and docosanoid signaling and metabolism in a murine model of contact hypersensitivity

Abstract

Abstract. Poly(ADP-ribose) polymerase (PARP)-1 is a pro-inflammatory protein. The inhibition of PARP-1 reduces the activity of numerous pro-inflammatory transcription factors, which results in the reduced production of pro-inflammatory cytokines, chemokines, matrix metalloproteinases and inducible nitric oxide synthase, culminating in reduced inflammation of the skin and other organs. The aim of the present study was to investigate the effects of the deletion of PARP-1 expression on polyunsaturated fatty acids (PUFA), and PUFA metabolite composition, in mice under control conditions or undergoing an oxazolone (OXA)-induced contact hypersensitivity reaction (CHS). CHS was elicited using OXA in both the PARP-1 +/+ and PARP-1 �/� mice, and the concentration of PUFAs and PUFA metabolites in the diseased skin were assessed using lipidomics experiments. The levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were shown to be increased in the PARP-1 �/� mice, as compared with the control, unsensitized PARP-1 +/+ mice. In addition, higher expression levels of fatty acid binding protein 7 (FABP7) were detected in the PARP-1 �/� mice. FABP7 is considered to be a specific carrier of DHA and EPA. Furthermore, the levels of the metabolites of DHA and EPA (considered mainly as anti-inflammatory or pro-resolving factors) were higher, as compared with the metabolites of arachidonic acid (considered mainly pro-inflammatory), both in the unsensitized control and OXA-sensitized PARP-1 �/� mice. The results of the present study suggest that the genetic deletion of PARP-1 may affect the PUFA-homeostasis of the skin, resulting in an anti-inflammatory milieu, including increased DHA and EPA levels, and DHA and EPA metabolite levels. This may be an important component of the anti-inflammatory action of PARP-1 inhibition.

The role of ADP-ribose metabolism in metabolic regulation, adipose tissue differentiation, and metabolism

“…Erener et al (2012b) reported hypercholesterolaemia in PARP1 knockout mice. The pattern of polyunsaturated fatty acid metabolites is dysregulated in PARP1 knockout mice (Kiss et al 2015) and there seems to be a correlation between PARP1 activity and erythrocyte membrane composition (Bianchi et al 2016). Furthermore, the composition of membrane-constituent lipids was altered upon the deletion of PARP2 (Marton et al 2018b).…”

“…For example, the deletion of PARP2 reduces the expression of fatty acid synthase in the white adipose tissue (Bai et al 2007). The expression of the fatty acid transporters, FABP7, FABP3, CD36, and aP2 (FABP4), are regulated by PARP1, PARP2, and tankyrases (Bai et al 2007;Yeh et al 2009;Erener et al 2012a;Kiss et al 2015). The deletion of PARP1, PARP2, or PARP10 induces mitochondrial fatty acid oxidation (Bai et al 2011a,b;Márton et al 2018a).…”

Poly(ADP-Ribose) Polymerases in Aging - Friend or Foe?

“…white adipose tissue) that on the long run deteriorates the function of these tissues, while on the other, the elimination of pathogens is limited. PARP-1 and PARP-2 control the expression of a plethora of chemokines, cytokines, inducible nitric oxide synthase (iNOS) and polyunsaturated fatty acids and exert proinflammatory roles in Th1 and Th2-mediated pathologies [65,66]. It is tempting to speculate that ageing-related enhancement of PARP activity may feed-forward the low grade inflammation that accompanies inflammaging.…”

A Case Study of Familiar Gastrointestinal Pathologies at Risk of Cancer. Early Detection of Degenerative Signals by Oxidative Stress Biomarkers

“…A natural adaptation response is active and the appropriate changes of the FAs microenvironment ensure the best functioning of membrane proteins, receptors, pumps and signals in tissues, according to environmental and metabolic needs [22].The important role of changes to the membrane structure and corresponding physical-chemical properties are well established [23]. A recent report gave evidence that PARP-1 ablation alters eicosanoid and docosanoid signaling and metabolism in a murine model of contact hypersensitivity [24]. Moreover both molecular events drive epigenetic mechanisms [25].…”