Unexpected Anticancer Activity of the E-Peptide of Rainbow Trout Pro-IGF-I

Marine OMICS ◽  
2016 ◽  
pp. 347-381
Author(s):  
Thomas T. Chen ◽  
Maria J. Chen ◽  
Jay H. Lo ◽  
Chun-Mean Lin
Keyword(s):  
Rainbow Trout ◽  
Anticancer Activity ◽  
Igf I

Insulin and insulin-like growth factor I signaling pathways in rainbow trout (Oncorhynchus mykiss) during adipogenesis and their implication in glucose uptake

2010 ◽  
Vol 299 (1) ◽  
pp. R33-R41 ◽  
Author(s):  
L. Bouraoui ◽  
E. Capilla ◽  
J. Gutiérrez ◽  
I. Navarro
Keyword(s):  
Rainbow Trout ◽  
Growth Factor ◽  
Oncorhynchus Mykiss ◽  
Glucose Uptake ◽  
Signaling Pathways ◽  
Mapk Phosphorylation ◽  
Factor I ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Igf I ◽  
Stimulation Of

Primary cultures of rainbow trout ( Oncorhynchus mykiss ) adipocytes were used to examine the main signaling pathways of insulin and insulin-like growth factor I (IGF-I) during adipogenesis. We first determined the presence of IGF-I receptors (IGF-IR) and insulin receptors (IR) in trout preadipocytes ( day 5) and adipocytes ( day 14). IGF-IRs were more abundant and appeared to be in higher levels in differentiated cells than in preadipocytes, whereas IRs were detected in lower but constant levels throughout the culture. The cells were immunoreactive against ERK1/2 MAPK, and AKT/PI3K, components of the two main signal transduction pathways for insulin and IGF-I receptors. Stimulation of MAPK phosphorylation by IGF-I was higher in preadipocytes than in adipocytes, while no effects were observed in MAPK phosphorylation after incubation of cells with insulin. AKT phosphorylation increased in the presence of both insulin and IGF-I, with higher levels of stimulation in adipocytes than in preadipocytes. Activation of both pathways was blocked by the use of specific inhibitors of MAPK (PD98059) and AKT (wortmannin). We describe here, for the first time, the effects of IGF-I and insulin on 2-deoxyglucose uptake in primary culture of trout adipocytes. IGF-I was more potent in stimulating glucose uptake than insulin, and PD98059 and wortmannin inhibited the stimulation of glucose uptake by this growth factor, suggesting that IGF-I plays an important metabolic role in trout adipocytes. Our results suggest that differential activation of the MAPK and AKT pathways are involved in the IGF-I- and insulin-induced effects of trout adipocytes during the various stages of adipogenesis.

Effects of insulin-like growth factor-I, insulin, and leucine on protein turnover and ubiquitin ligase expression in rainbow trout primary myocytes

2010 ◽  
Vol 298 (2) ◽  
pp. R341-R350 ◽  
Author(s):  
Beth M. Cleveland ◽  
Gregory M. Weber
Keyword(s):  
Protein Synthesis ◽  
Rainbow Trout ◽  
Growth Factor ◽  
Protein Degradation ◽  
Ubiquitin Ligase ◽  
Protein Turnover ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

The effects of insulin-like growth factor-I (IGF-I), insulin, and leucine on protein turnover and pathways that regulate proteolytic gene expression and protein polyubiquitination were investigated in primary cultures of 4-day-old rainbow trout myocytes. Supplementing media with 100 nM IGF-I increased protein synthesis by 13% ( P < 0.05) and decreased protein degradation by 14% ( P < 0.05). Treatment with 1 μM insulin increased protein synthesis by 13% ( P < 0.05) and decreased protein degradation by 17% ( P < 0.05). Supplementing media containing 0.6 mM leucine with an additional 2.5 mM leucine did not increase protein synthesis rates but reduced rates of protein degradation by 8% ( P < 0.05). IGF-I (1 nM–100 nM) and insulin (1 nM-1 μM) independently reduced the abundance of ubiquitin ligase mRNA in a dose-dependent manner, with maximal reductions of ∼70% for muscle atrophy F-box (Fbx) 32, 40% for Fbx25, and 25% for muscle RING finger-1 (MuRF1, P < 0.05). IGF-I and insulin stimulated phosphorylation of FOXO1 and FOXO4 ( P < 0.05), which was inhibited by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin, and decreased the abundance of polyubiquitinated proteins by 10–20% ( P < 0.05). Supplementing media with leucine reduced Fbx32 expression by 25% ( P < 0.05) but did not affect Fbx25 nor MuRF1 transcript abundance. Serum deprivation decreased rates of protein synthesis by 60% ( P < 0.05), increased protein degradation by 40% ( P < 0.05), and increased expression of all ubiquitin ligases. These data suggest that, similar to mammals, the inhibitory effects of IGF-I and insulin on proteolysis occur via P I3-kinase/protein kinase B signaling and are partially responsible for the ability of these compounds to promote protein accretion.

scholarly journals Biochemical and functional analysis of a conserved IGF-binding protein isolated from rainbow trout (Oncorhynchus mykiss) hepatoma cells

2001 ◽  
Vol 170 (3) ◽  
pp. 619-628 ◽  
Author(s):  
◽  
A Garmong ◽  
P Swanson ◽  
J Moore ◽  
M Lin ◽  
...  
Keyword(s):  
Rainbow Trout ◽  
Oncorhynchus Mykiss ◽  
Hepatoma Cells ◽  
Dependent Manner ◽  
High Sequence Identity ◽  
Concentration Dependent Manner ◽  
Igf Binding Proteins ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Igf I ◽  
Igf Binding

Rainbow trout (Oncorhynchus mykiss) serum contains several IGF-binding proteins (IGFBPs) that specifically bind to IGFs. The structures of these fish IGFBPs have not been determined and their physiological functions are poorly defined. In this study, we identified a 30 kDa IGFBP present in rainbow trout serum and secreted by cultured trout hepatoma cells. This IGFBP binds to IGFs but not to insulin. This IGFBP was purified to homogeneity using a three-step procedure involving Phenyl-Sepharose chromatography, IGF-I affinity chromatography and reverse-phase HPLC. Affinity cross-linking studies indicated that this IGFBP binds to IGF-I with a higher affinity than to IGF-II. N-terminal sequence analysis of the trout IGFBP suggests that it shares high sequence identity with that of human IGFBP-1 in the N-terminal region. When added to cultured fish and human cells, the trout IGFBP inhibited IGF-I-stimulated DNA synthesis and cell proliferation in a concentration-dependent manner. The inhibitory effect of the fish IGFBP was comparable to those of human IGFBP-1 and -4. These results indicate that the IGFBP molecule is structurally and functionally conserved in evolutionarily ancient vertebrate species such as bony fish.

Regulation of cartilage glycosaminoglycan synthesis in the rainbow trout, Oncorhynchus mykiss, by 3,3′,5-tri-iodo-l-thyronine and IGF-I

1996 ◽  
Vol 149 (2) ◽  
pp. 357-365 ◽  
Author(s):  
Y Takagi ◽  
B Th Björnsson
Keyword(s):  
Rainbow Trout ◽  
Oncorhynchus Mykiss ◽  
Thymidine Uptake ◽  
Post Injection ◽  
Sulfate Uptake ◽  
Glycosaminoglycan Synthesis ◽  
Sulfated Glycosaminoglycan ◽  
Igf I ◽  
Dose Dependent

Abstract The actions of 3,3′,5-tri-iodo-l-thyronine (T3) and recombinant human IGF-I (rhIGF-I) as well as their interaction on cartilage growth in rainbow trout (Oncorhynchus mykiss) were examined. Uptake of 3H-methyl thymidine and 35S-sulfate by isolated branchial cartilage was measured as a marker for chondrocyte proliferation and sulfated glycosaminoglycan synthesis respectively. When T3 (1·0 μg/g) was injected intraperitoneally, plasma T3 levels reached a transient peak after 1 day and decreased rapidly thereafter. Sulfate and thymidine uptake were not affected by T3 at 1 and 3 days post-injection, but at 6 days post-injection both were significantly higher in T3injected fish than those in controls. The stimulatory effects of a T3 injection on sulfate and thymidine uptake were dose-dependent over the range of 0·01, 0·1 and 1·0 μg/g. In vitro exposure of cartilage to T3 (0·075, 0·75, 7·5, 75 and 750 nm) for 6 days resulted in dose-dependent stimulation of sulfate uptake, with a maximum response at 7·5 nm and higher. T3 exposure (7·5 nm) for 2 or 3 days also increased sulfate uptake, but only slightly. Thymidine uptake was not clearly affected by T3. In vitro addition of rhIGF-I (0·075, 0·75 and 7·5 nm) increased sulfate uptake, but not thymidine uptake, dose-dependently. Compared with T3, rhIGF-I induced a greater maximum level of sulfate uptake: at 7·5 nm rhIGF-I increased the uptake 17-fold whereas T3 increased the uptake fourfold. When T3 (0·075, 0·75 or 7·5 nm) and rhIGF-I (0·1 or 1·0 nm) were added together, stimulative actions of T3 on sulfate uptake were largely additive to those of rhIGF-I. The results indicate that T3 as well as IGF-I are important modulators of sulfated glycosaminoglycan synthesis in rainbow trout cartilage. Journal of Endocrinology (1996) 149, 357–365

scholarly journals Compensatory Response of the Somatotropic Axis from IGFBP-2b Gene Editing in Rainbow Trout (Oncorhynchus mykiss)

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1488
Author(s):  
Beth M. Cleveland ◽  
Shiori Habara ◽  
Jin Oikawa ◽  
Lisa M. Radler ◽  
Munetaka Shimizu
Keyword(s):  
Rainbow Trout ◽  
Growth Factor ◽  
Gene Editing ◽  
Serum Insulin ◽  
Local Level ◽  
Expression Patterns ◽  
Inhibitory Response ◽  
Insulin Like Growth Factor ◽  
Compensatory Response ◽  
Igf I

Rainbow trout with gene editing-induced reductions in serum insulin-like growth factor binding protein (IGFBP)-2b exhibit similar growth performance compared to fish without IGFBP-2b gene disruption. The objective of this study is to determine how the components of the insulin-like growth factor (IGF)/IGFBP system respond to a reduction in serum IGFBP-2b abundance. Editing the IGFBP-2b genes in rainbow trout resulted in an 83% decrease in serum IGFBP-2b in mutants. This resulted in a 35% reduction in serum IGF-I, which was offset by reduced expression of hepatic igfbp-1a2 and increased muscle igfr-1a; these responses suggest that an increased IGF-I signaling capacity offset reductions in serum IGF-I. During feed deprivation, the differential expression of igfbp genes supports the attenuation of the growth inhibitory response, likely due to the further reduction in serum IGF-I that alleviated the need for an IGF-inhibitory response. Unique igfbp expression patterns occurred during refeeding, suggesting an enhanced IGF-I signaling capacity in controls. Collectively, these findings support that the role of IGFBP-2b is to regulate serum IGF-I concentrations. The compensatory regulation of IGF/IGFBP system genes indicates that adjustments in other IGFBP, both circulating and at the local level, maintain IGF-I signaling at a level appropriate for the nutritional state of the fish.

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