title: Cryptosporidium parvum induces an endoplasmic stress response in the intestinal adenocarcinoma HCT-8 cell line.
abstract: Invasion of human intestinal epithelial cells (HCT-8) by Cryptosporidium parvum resulted in a rapid induction of host cell spermidine/spermine N(1)-acetyltransferase 1 (hSSAT-1) mRNA, causing a 4-fold increase in SSAT-1 enzyme activity after 24 h of infection. In contrast, host cell SSAT-2, spermine oxidase, and acetylpolyamine oxidase (hAPAO) remained unchanged during this period. Intracellular polyamine levels of C. parvum-infected human epithelial cells were determined, and it was found that spermidine remained unchanged and putrescine increased by 2.5-fold after 15 h and then decreased after 24 h, whereas spermine decreased by 3.9-fold after 15 h. Concomitant with these changes, N(1)-acetylspermine and N(1)-acetylspermidine both increased by 115- and 24-fold, respectively. Increased SSAT-1 has previously been shown to be involved in the endoplasmic reticulum (ER) stress response leading to apoptosis. Several stress response proteins were increased in HCT-8 cells infected with C. parvum, including calreticulin, a major calcium-binding chaperone in the ER; GRP78/BiP, a prosurvival ER chaperone; and Nrf2, a transcription factor that binds to antioxidant response elements, thus activating them. However, poly(ADP-ribose) polymerase, a protein involved in DNA repair and programmed cell death, was decreased. Cumulatively, these results suggest that the invasion of HCT-8 cells by C. parvum results in an ER stress response by the host cell that culminates in overexpression of host cell SSAT-1 and elevated N(1)-acetylpolyamines, which can be used by a parasite that lacks ornithine decarboxylase.
authors.affiliation: From Haskins Laboratories and.
authors.forename: Mary
authors.initials: M
authors.lastname: Morada
authors.affiliation: the Roswell Park Cancer Research Institute, Buffalo, New York 14263, and.
authors.forename: Lakhsmi
authors.initials: L
authors.lastname: Pendyala
authors.affiliation: From Haskins Laboratories and.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: the Fels Institute of Cancer Research and Molecular Biology and the Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
authors.forename: Salim
authors.initials: S
authors.lastname: Merali
authors.affiliation: From Haskins Laboratories and; the Department of Chemistry and Physical Sciences, Pace University, New York, New York 10038,. Electronic address: nyarlett@pace.edu.
authors.forename: Nigel
authors.initials: N
authors.lastname: Yarlett
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D017209:Apoptosis; D037282:Calreticulin / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003457:Cryptosporidiosis / Q000235:genetics / Q000378:metabolism*; D016785:Cryptosporidium parvum / Q000235:genetics / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011700:Putrescine / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D037282:Calreticulin; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D051267:NF-E2-Related Factor 2; D009363:Neoplasm Proteins; D011700:Putrescine; D013095:Spermidine; D000099228:Diamine N-Acetyltransferase; C576483:CALR protein, human; C000717247:HSPA5 protein, human; C495635:NFE2L2 protein, human
keywords: Apoptosis; C. parvum; Endoplasmic Reticulum Stress; Host-Pathogen Interactions; Parasitology; Polyamines; SSAT; Unfolded Protein Response