Faculty Opinions recommendation of Effect of IGF-I on Hair Growth Is Related to the Anti-Apoptotic Effect of IGF-I and Up-Regulation of PDGF-A and PDGF-B.

The neuronal damage caused by ischemic brain injury is associated with increased apoptosis. IGF-I exposure promotes neuronal defense and survival against ischemic insult by inhibiting apoptotic processes. We investigated the role of prostate apoptosis response-4 (Par-4), a proapoptotic gene the expression of which is increased after ischemic injury, in IGF-I-mediated inhibition of apoptosis using PC12 cells exposed to oxygen–glucose deprivation (OGD). The OGD insult resulted in significant increases in apoptotic cell death and Par-4 expression, which were prevented by the treatment of cells with an antisense oligonucleotide of Par-4. IGF-I treatment prior to OGD insult significantly reduced the number of apoptotic cells and the OGD-induced increase in Par-4 expression. OGD-induced nuclear translocation of Par-4 was also attenuated by IGF-I treatment. In addition, we demonstrated that the anti-apoptotic effect of IGF-I was blocked by chemical inhibition of a mitogen activated protien kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), or protein kinase A (PKA), but not by a protein kinase C inhibitor. Finally, pretreatment of cells with a MAPK or PI3K inhibitor attenuated IGF-I-induced inhibition of Par-4 expression, suggesting that the MAPK and PI3K pathways contribute to IGF-I-induced Par-4 suppression. In contrast, a PKA inhibitor failed to alter the inhibitory effect of IGF-I on Par-4. These findings indicate that in PC12 cells exposed to OGD insult, IGF-I protects cells from apoptosis, at least in part through the inhibition of Par-4 expression.

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46 ANTI-APOPTOTIC EFFECT OF INSULIN-LIKE GROWTH FACTOR-1 AND ITS RECEPTOR ON DEVELOPMENT OF PORCINE PRE-IMPLANTATION EMBRYOS PRODUCED BY IN VITRO FERTILIZATION AND SOMATIC CELL NUCLEAR TRANSFER

Reproduction Fertility and Development ◽

10.1071/rdv18n2ab46 ◽

2006 ◽

Vol 18 (2) ◽

pp. 132

Author(s):

S. Kim ◽

S. H. Lee ◽

J. H. Kim ◽

Y. W. Jeong ◽

O. J. Koo ◽

...

Keyword(s):

Growth Factor ◽

Embryo Development ◽

Developmental Competence ◽

Insulin Like Growth Factor ◽

Mammalian Embryo ◽

Vitro Fertilization ◽

Igf I ◽

Apoptotic Effect ◽

Bax Gene

Insulin-like growth factor (IGF)-I is a receptor-mediated autocrine and/or paracrine growth and/or survival factor for mammalian embryo development. It is known to promote the growth and development of mouse pre-implantation embryos. The present study was designed to investigate the effects of IGF-I (50 ng/mL), anti-IGF-I receptor (IGR-IR) antibody (0.05 �g/mL), and their combination on porcine pre-implantation embryo development. Furthermore, the mechanism underlying the embryotropic effects of IGF-I was evaluated by monitoring the incidence of apoptosis and expression of apoptosis-related genes. In both IVF and SCNT embryos, culturing with IGF-I increased the rate of blastocyst formation and this embryotropic effect was neutralized by culturing with IGF-I and anti-IGF-I receptor antibody. Significant effects on the development of blastocysts (P < 0.05) were found in IVF (16.9, 22.6, 9.3, and 13.5% for control, IGF-I, anti-IGF-IR antibody, and their combination, respectively) and SCNT (13.2, 21.0, 5.4, and 15.7%) embryos. Culturing IVF and SCNT embryos with IGF-I significantly increased the total number of cells in IVF blastocysts (58.3, 72.4, 41.1, and 55.2; P < 0.05), and SCNT blastocysts (49.2, 60.1, 35.2, and 43.1; P < 0.05), and it decreased the number of apoptotic nuclei in IVF blastocysts (3.9, 2.8, 5.5, and 3.9; P < 0.05) and SCNT blastocysts (4.6, 3.0, 6.1, and 4.9; P < 0.05). These effects of IGF-I were also neutralized by culturing with IGF-I along with anti-IGF-IR antibody. Expression of the anti-apoptotic Bcl-2 gene was increased, whereas expression of the pro-apoptotic Bax gene was decreased in both IVF and SCNT embryos cultured with IGF-I. In both IVF and SCNT embryos, anti-IGF-IR antibody along with IGF-I neutralized the effect of IGF-I on expression of Bcl-2 and Bax genes. In conclusion, the present study demonstrated that IGF-I through its specific receptors improved the developmental competence of IVF and SCNT embryos by decreasing the incidence of apoptosis and regulating apoptosis-related genes in porcine pre-implantation embryos. This study was supported by grants from the Korean MOST (Top Scientist Fellowship) and MAF (Biogreen 21 #20050301-034-443-026-01-00).

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