Establishing a role for shrimp fortilin in preventing cell death Potchanapond Graidist a , Kenichi Fujise b , Warapond Wanna a , Kallaya Sritunyalucksana c , Amornrat Phongdara a, ⁎ a Department of Biochemistry, Faculty of Science, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand b Research Center for Cardiovascular Disease, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Disease and Division of Cardiology, Department of Internal Medicine, The University of Texas-Houston Health Science Center, Houston, Texas 77030, USA c Centex Shrimp, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand Received 6 September 2005; received in revised form 15 December 2005; accepted 15 December 2005 Abstract White spot syndrome virus (WSSV) is a highly virulent and infectious virus to farmed shrimps and represents a serious threat to aquatic industries. Fortilin, also known as translationally controlled tumor protein (TCTP), protects mammalian cells under stress from cell death. A subtraction hybridization screening in our laboratory between healthy and moribund WSSV-infected Penaeus mondon shrimps has identified a fortilin gene whose messages critically decrease during the terminal stage of the WSSV-induced illness. Fortilin/TCTPs are highly conserved throughout the animal and plant kingdoms, and shrimp fortilin has a 64% identity in amino acid composition with human fortilin. In our previous work, the data clearly suggested that fortilin in shrimp protected WSSV-infected shrimps from death. Although human fortilin has a role in apoptosis regulation, it is not known if shrimp fortilin has any role in apoptosis regulation. We report that fortilin is greatly upregulated in shrimp haemolymph during the early phase of WSSV infection and that its expression abruptly decreases as the shrimp becomes moribund. Strikingly, shrimp fortilin, when overexpressed in mammalian cells, protected them from cell death induced by etoposide, staurosporine, cisplatin, hydroxyurea, and 5-fluorouracil (5-FU). These data suggest that shrimp fortilin, like mammalian fortilin, can protect cells under toxic conditions from death. In addition, since shrimp fortilin was capable of protecting cells in a mammalian environment, this indicates that shrimp and human fortilin use a common cellular pathway to achieve this. Shrimp fortilin may play a critical role in their response to WSSV- infection, through regulation of a cell death pathway that is common to shrimp and humans. © 2006 Elsevier B.V. All rights reserved. Keywords: Penaeus monodon (Pm); White spot syndrome virus (WSSV); Anti-apoptotic protein; Fortilin; Translationally controlled tumor protein (TCTP) 1. Introduction In the past decade, white spot syndrome virus (WSSV) has been the most serious viral disease of farmed penaeid shrimp (Zhang et al., 2002b). Once introduced, the virus spreads rapidly and infects other species of aquatic organisms including crabs and crayfish (Chen et al., 1997; Flegel, 1997; Lo et al., 1996). The crustacean immune response can be divided into cellular and humoral components. The cellular compo- nent is related to haemocytes, that are involved in immediate defensive reactions such as nodulation, encap- sulation and phagocytosis. The humoral component Aquaculture 255 (2006) 157 – 164 www.elsevier.com/locate/aqua-online ⁎ Corresponding author. Tel./fax: +66 74 288384. E-mail address: pamornra@yahoo.com (A. Phongdara). 0044-8486/$ - see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.aquaculture.2005.12.023