Stress (Physiology)

Fibropapillomatosis (FP) is a devastating pandemic characterized by benign
cutaneous neoplasias that is afflicting marine turtles worldwide. This study evaluated the
expression of HSP72, GRP96, and Bcl-2 in tumor and healthy biopsies. These proteins
are found in high levels in some tumors and prevent apoptosis, allowing tumor cells to
survive. HSP72 and GRP96 are also known to initiate an immune response and may
contribute to the regression often observed in FP tumors. Results were found that
showed all three protective proteins had significantly higher levels in actively growing
tumor tissue compared to healthy tissue. Specifically, cauliflower-like tumors, thought to
be actively growing, were found to have higher levels of HSP72 and GRP96 compared to
healthy skin, whereas smooth tumors, thought to be regressing, did not. These results
offer insight into the molecular mechanisms behind the development of FP tumors and
open a number of avenues for future research.

It is well established that altered neurotransmitter levels have long been associated with stress in many mammals. The purpose of this study was to determine if changes in the brain tissue concentration and/or turnover rates of the monoamine neurotransmitters could be used as an early indicator of physiological stress for fish in different aquatic ecosystems. Gray snapper, Lutjanus griseus, were collected from two sites, a pristine (control) and a polluted (experimental) site, classification based upon the hydrocarbon content of their sediment. The brains were quickly removed and dissected into three regions: frontal lobes, hypothalamus, and brain stem which were later analyzed for using high performance liquid chromatography. A decrease in brain tissue norepinephrine and dopamine concentration in the frontal lobes and hypothalamus was observed in individuals collected from the polluted site. No significant difference in either norepinephrine or dopamine concentration was present in the brain stem. Despite a decrease in dopamine levels, there was no significant change in dopamine turnover. There was a significant decrease in serotonin concentration in the hypothalamus at the polluted site. There was an increase in serotonergic activity in the hypothalamus and brain stem at the polluted site. A significant decrease in the weight of the hypothalamus in fish from the polluted site was also observed. These results suggest that a change in brain monoamines can be used as a early indicators of chronic environmental stress.

Green turtle fibropapillomatosis (GTFP) is a highly debilitating disease that affects several species of marine turtles worldwide. This study evaluated stress protein expression in red blood cells (RBCs), skin and tumors of green turtles (Chelonia mydas) from a GTFP-prevalent site and a more pristine, GTFP-free site. Levels of expression of HSP72 were significantly higher in healthy turtles from the GTFP-prevalent site compared to healthy turtles from the GTFP-free site, suggesting that these turtles are, indeed stressed. Levels of HSP72 expression were also significantly higher in the nucleated RBCs than in skin tissues of turtles from both sites. These results demonstrate the utility of RBC stress protein evaluation as a new, minimally invasive method of evaluating stress loads in marine turtles as a factor in the potentially multifactorial etiology of GTFP. In addition, HSP72 and GP96 were present and detectable in tumors of diseased turtles, and thus show potential for use in treatment of GTFP.

We attempted to understand the molecular regulators that impact inflammation using a rat model of human sensation-seeking/risk-taking trait for drug and stress vulnerability, based on their exploratory behavior displaying high rates (HRs) or low rates of locomotor reactivity (LRs) to environmental stress. We found that HRs have a pro-inflammatory phenotype as indicated by increased protein expression of the inflammatory cytokine TNF-(Sa(B. Furthermore, we found that HRs have a lower gene expression of the glucocorticoid receptor and histone deacetylase 2 which are known to play an immunosuppressive role. Autophagy (macroautophagy) is a homeostatic process needed for cell maintenance, growth and proliferation and known to assist in tumor survival. FYVE and coiled-coil domain containing 1 (FYCO1) is a novel protein implicated to assist in the plus-end directed trafficking and fusion of autophagosomes. In these studies, we show that FYCO1 gene expression among human breast cell lines of varying degrees of malignancy.

Sponges are an important source of bioactive marine natural products, or secondary metabolites. The common Caribbean reef sponge, Axinella corrugata, produces an antitumor and antibacterial chemical, stevensine. This study determined whether environmental stressors, such as elevated temperature and exposure to Amphibalanus amphitrite larvae, affect the production of stevensine by A.corrugata and if the stressors caused A.corrugata to exhibit differential gene expression. Temperature stress resulted in no significant change in the production of stevensine; only two genes were significantly differentially expressed, including hsp70. Larval stressed resulted in increased production of stevensine and significant differential gene expression (more than seventy genes). This study suggests that A.corrugata may be resilient to elevations in temperature and that one of stevensine's roles in nature is as an antifoulant.

Human mesenchymal stem cells (MSCs) are being evaluated for the treatment of a broad array of diseases due to their ability to secrete a variety of therapeutically beneficial paracrine-acting factors. For example, MSC conditioned media (MSC-CM) has been shown to inhibit hypoxia-induced apoptosis in human aortic endothelial cells (HAECs) via activation of the P13-AKT pathway. However, the factors secreted by MSCs responsible for this effect have yet to be identified. Recent studies have shown that the glycoprotein Follistatin-like 1 (FSTL1) activates the P13-AKT pathway by binding to the receptor disco-interacting protein (DIP2A) expressed on the surface of cells. Based on our data indicating that MSCs constitutively secrete high quantities of FSTL1, we hypothesize that this protein principally mediates the anti-apoptopic effect of MSC-CM on HAECs. Loss-of-function studies employing siRNA-mediated knockdown of the protein and neutralizing antibodies will be used to assess the role of FSTL1 in growth and survival of HAECs following exposure to hypoxic stress.