Matrix metalloproteinase-7 inhibitory activity of lipid extract from dwarf gulper shark (Centrophorus atromarginatus) through down- regulation of gene transcription Kazuhiro Shiozaki a,b,⇑ , Minori Yoshikawa a , Saori Kiguchiya a , Asami Ikeda a , Yuko Kamada a , Petros Kingstone Chigwechokha b , Masaharu Komatsu a,b a Faculty of Fisheries, Kagoshima University, Kagoshima 890-0056, Japan b The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima 890-0056, Japan article info Article history: Received 20 June 2016 Received in revised form 4 January 2017 Accepted 5 January 2017 Keywords: c-jun Dwarf gulper shark Ganglioside MMP-7 Zymography abstract Deep-sea living dwarf gulper shark (Centrophorus atromarginatus) is industrially important resource with lots of squalene in the liver, used as the resource for cosmetic ingredients, while consumption of shark muscle is limited because of ammonia smell caused by bacterial urease. Here, effect of shark muscle lipid on matrix metalloproteinase-7 (MMP-7) activity was estimated to develop the new application of shark muscle. Treatment of shark lipid toward HT-29 cells attenuated MMP-7 activity in conditioned medium accompanied with its decreased extracellular secretion. Ganglioside types in shark lipid were investi- gated by thin layer chromatography. Among shark gangliosides, GD1a and GM1 attenuated MMP-7 activ- ity. GD1a negatively regulated MMP-7 polypeptide and its gene expression in HT-29 cells, whereas MAPKs signaling pathways were not altered. GD1a suppressed c-jun expression in HT-29 cells, which could negatively regulate mmp-7 transcription. This study indicated the possibility of dwarf gulper shark muscle as a material of functional food. Ó 2017 Elsevier Ltd. All rights reserved. 1. Introduction Dwarf gulper shark (Centrophorus atromarginatus) lives in the deep-sea and is caught around Nansei Islands in Japan. In general, deep-sea living shark is a useful biological resource because of high amount of squalene obtained from the liver (Bakes & Nichols, 1995). Squalane is industrially converted from squalene by hydro- gen addition and then used for the ingredients of cosmetics. Hence, dwarf gulper shark is caught and its liver is used to extract the liver oil. On the other hand, most portion of dwarf gulper shark muscle is a processing waste. Unfortunately, the muscle immediately develops a bad smell as the freshness decreases. Shark muscle con- tains plenty of urea which changes to ammonia by bacterial urease. At the moment, the consumption of dwarf gulper shark muscle as food is limited in some place, such as Nansei Islands. People in Nansei Islands are famous with long life span, and it has been suggested that their local foods are an important compo- nent for their healthy life (Mimura et al., 2004). To investigate the utilization of dwarf gulper shark muscle, its application as func- tional food is thought to be useful. Previous study revealed that hydrolysates of the dwarf gulper shark muscle, prepared using food-processing proteinase, exhibit antihypertensive and antioxi- dant activity and that Val-Trp was identified as a potent peptide in the hydrolysate (Ikeda et al., 2015). It has been reported that shark muscle oil shows inhibition pro-angiogenic activity accom- panied with a decrease of vascular endothelial growth factor recep- tor (VEGFR) (Yuan, Yoshida, & Davis, 2006; Yuan, Ahn, & Davis, 2007). However, little is known about healthy functions derived from shark muscle different from shark liver and cartilage. MMP-7 (matrilysin) is one of the metalloproteinases (MMPs) which are zinc- or calcium containing endopeptidases. MMP-7 is involved in lung cancer cell proliferation (Liu et al., 2007), gastric and colon tumor differentiation (McDonnell, Navre, Coffey, & Matrisian, 1991), diabetes (Ban et al., 2010), solar-damaged skin induction (Saarialho-Kere et al., 1999) and immuno response http://dx.doi.org/10.1016/j.jff.2017.01.013 1756-4646/Ó 2017 Elsevier Ltd. All rights reserved. Abbreviations: BSA, bovine serum albumin; FBS, fetal bovine serum; MMP, matrix metalloproteinase. ⇑ Corresponding author at: 4-50-20 Shimoarata, Kagoshima 890-0056, Japan. E-mail addresses: shiozaki@fish.kagoshima-u.ac.jp (K. Shiozaki), k6617342@ kadai.jp (M. Yoshikawa), k1232520@kadai.jp (S. Kiguchiya), a-ikeda@jm.kuas. kagoshima-u.ac.jp (A. Ikeda), kedama@fish.kagoshima-u.ac.jp (Y. Kamada), pchigwe@yahoo.com (P.K. Chigwechokha), komatsu@fish.kagoshima-u.ac.jp (M. Komatsu). Journal of Functional Foods 30 (2017) 90–96 Contents lists available at ScienceDirect Journal of Functional Foods journal homepage: www.elsevier.com/locate/jff