Bioprospecting function of an ancient gene (CRTAC) encoding a novel protein in a marine teleost by comparative analysis

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Chronic stress impairs the local immune response during cutaneous repair in gilthead sea bream (Sparus aurata, L.)

Publication . Mateus, Ana; Anjos, Liliana; Cardoso, João CR; Power, Deborah

Scale removal in fish triggers a damage-repair program to re-establish the lost epidermis and scale and an associated local immune response. In mammals, chronic stress is known to delay wound healing and to modulate the cutaneous stress axis, but this is unstudied in teleost fish the most successful extant vertebrates. The present study was designed to test the hypothesis that chronic stress impairs cutaneous repair in teleost fish as a consequence of suppression of the immune response. The hypothesis was tested by removing the scales and damaging the skin on one side of the body of fish previously exposed for 4 weeks to a chronic crowding stress and then evaluating cutaneous repair for 1 week. Scale removal caused the loss of the epidermis although at 3 days it was re-established. At this stage the basement membrane was significantly thicker (p = 0.038) and the hypodermis was significantly thinner (p = 0.016) in the regenerating skin of stressed fish relative to the control fish. At 3 days, stressed fish also had a significantly lower plasma osmolality (p = 0.015) than control fish indicative of reduced barrier function. Chronic stress caused a significant down-regulation of the glucocorticoid receptor (gr) in skin before damage (time 0, p = 0.005) and of star at 3 and 7 days (p < 0.05) after regeneration relative to control fish. In regenerating skin key transcripts of cutaneous repair, pcna, colival and nunp9, and the inflammatory response, tgf beta 1, mpo and crtac2, were down-regulated (p < 0.05) by chronic stress. Irrespective of chronic stress and in contrast to intact skin many hyper pigmented masses, putative melanomacrophages, infiltrated the epidermis of regenerating skin. This study reveals that chronic stress suppresses the local immune response to scale removal and impairs the expression of key transcripts of wound healing. Elements of the stress axis were identified and modulated by chronic stress during cutaneous repair in gilthead seabream skin.

2017-07Journal article

Open access

Cartilage acidic protein 1, a new member of the beta-propeller protein family with amyloid propensity

Publication . Anjos, Lliana; Morgado, Isabel; Guerreiro, Marta; Cardoso, João CR; Melo, Eduardo; Power, Deborah

Cartilage acidic protein1 (CRTAC1) is an extracellular matrix protein of chondrogenic tissue in humans and its presence in bacteria indicate it is of ancient origin. Structural modeling of piscine CRTAC1 reveals it belongs to the large family of beta-propeller proteins that in mammals have been associated with diseases, including amyloid diseases such as Alzheimer's. In order to characterize the structure/function evolution of this new member of the beta-propeller family we exploited the unique characteristics of piscine duplicate genes Crtac1a and Crtac1b and compared their structural and biochemical modifications with human recombinant CRTAC1. We demonstrate that CRTAC1 has a beta-propeller structure that has been conserved during evolution and easily forms high molecular weight thermo-stable aggregates. We reveal for the first time the propensity of CRTAC1 to form amyloid-like structures, and hypothesize that the aggregating property of CRTAC1 may be related to its disease-association. We further contribute to the general understating of CRTAC1's and beta-propeller family evolution and function. Proteins 2017; 85:242-255. (c) 2016 Wiley Periodicals, Inc.

2017-02Journal article

Open access