Including Insulin-like Growth Factor 1 Research Articles

Gene therapy for ALS delivers

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease that kills motor neurons. Despite a long disappointing history of human trials with neurotrophins, including insulin-like growth factor 1 (IGF-1), Kaspar and colleagues have successfully slowed disease in transgenic ALS mice by forcing motor neurons to produce IGF-1 following retrograde delivery of recombinant adeno-associated virus (AAV) injected into muscle. With the clinical safety of both IGF-1 and AAV already established, this provides real hope for an effective treatment of ALS.

The investigation of short stature: a survey of practice in Wales and suggested practical guidelines

Aim: To survey the investigation of short stature in Wales and suggest guidelines to improve practice. Methods: Questionnaires were circulated to paediatricians and consultant clinical biochemists or consultant chemical pathologists...

Measurement of bone morphogenetic proteins and other growth factors in demineralized bone matrix.

Osteoinductivity of demineralized bone matrix has been attributed to bone morphogenetic proteins (BMP). Other growth factors, including insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta1 (TGF-beta1), have also been detected in demineralized bone matrix. Success of bone graft substitutes containing demineralized bone matrix has been assumed to be closely associated with osteoinductivity of the demineralized bone matrix. Because of differences in bone characteristics between donors and tissue banks, confirmation and measurement of osteoinductivity may play a crucial role in predicting the success of the bone graft substitute. In the current studies, BMP-2, BMP-4, TGF-beta1, and IGF-1 were measured in demineralized bone matrix. A strong association was noted between BMP-2 and TGF-beta1 levels. A strong association was also found between BMP-2 and new bone formation in an ectopic nude rat model.

Akt is a molecular target for signal transduction therapy in brain ischemic insult.

Growth factors including insulin-like growth factor-1 (IGF-1) promote cell survival in ischemic brain injury. Stimulation of IGF-1 receptor coupled with tyrosine kinase activates phosphatidylinositol 3-kinase and subsequently, protein kinase B (Akt) in hippocampal neurons. Here we introduce a new approach of signal transduction therapy for brain damage occurring in ischemic insult. As has been shown for IGF-1, intracerebroventricular injection of sodium orthovanadate, a protein tyrosine phosphatase inhibitor, prior to ischemic insult blocked delayed neuronal death in the CA1 region. The neuroprotective effects of orthovanadate and IGF-1 were associated with an increased Akt activity in the CA1 region. We discuss here potential targets for Akt relevant to such neuroprotective activity. Our findings lead to the conclusion that Akt activity is a potential target for neuroprotective drugs in brain ischemic insult and other episodes of excitotoxic neuronal apoptosis such as seizure and Huntington's and Parkinson's diseases.

Transcriptional and Translational Regulation of Angiotensin II Type 2 Receptor by Angiotensin II and Growth Factors

The regulatory effects of angiotensin-II (AngII) and several growth factors, including insulin-like growth factor 1 (IGF-1), basic fibroblast growth factor (bFGF), and transforming growth factor β1 (TGFβ1) on the AngII subtype 2 (AT2) receptor were studied using R3T3 cells, a mouse fibroblast cell line that expresses only AT2 receptors. AngII increased (in a time- and dose-dependent manner) AT2 binding sites but had no effects on AT2 messenger RNA (mRNA) levels. At maximal concentration (10−7m) AngII caused a 4-fold increase of AT2 receptor number. In contrast, IGF-1 increased (3- to 4-fold), whereas bFGF and TGFβ1 decreased (by about 90% and 80%, respectively) AT2 receptor and mRNA levels. Moreover, AngII potentiated the effect of IGF-1 on receptor number, but not on AT2 mRNA levels, and significantly reduced the inhibitory action of bFGF and TGFβ1 on AT2 binding sites but not on AT2 mRNA levels. None of these factors modified AT2 mRNA half-life. The potential effects of these factors on transcription of the AT2 gene were measured by means of nuclear run-on assays. IGF-1 increased the rate of transcription by about 2.5-fold, whereas bFGF and TGFβ1 reduced it by 90 and 80%, respectively. In contrast, AngII did not modify either the basal or IGF-1-stimulated transcription rate. Finally, AngII alone or together with IGF-1, but not IGF-1 alone, increased the attachment of AT2 mRNA to polysomal fractions. The present findings demonstrate that the main mechanism by which AngII regulates the AT2 receptor is by increasing the rate of AT2 mRNA translation, whereas the stimulatory (IGF-1) or inhibitory (bFGF and TGFβ1) effects of these growth factors on AT2 expression are exerted at the transcriptional level.

Transcriptional and translational regulation of angiotensin II type 2 receptor by angiotensin II and growth factors.

The regulatory effects of angiotensin-II (AngII) and several growth factors, including insulin-like growth factor 1 (IGF-1), basic fibroblast growth factor (bFGF), and transforming growth factor beta1 (TGFbeta1) on the AngII subtype 2 (AT2) receptor were studied using R3T3 cells, a mouse fibroblast cell line that expresses only AT2 receptors. AngII increased (in a time- and dose-dependent manner) AT2 binding sites but had no effects on AT2 messenger RNA (mRNA) levels. At maximal concentration (10(-7) M) AngII caused a 4-fold increase of AT2 receptor number. In contrast, IGF-1 increased (3- to 4-fold), whereas bFGF and TGFbeta1 decreased (by about 90% and 80%, respectively) AT2 receptor and mRNA levels. Moreover, AngII potentiated the effect of IGF-1 on receptor number, but not on AT2 mRNA levels, and significantly reduced the inhibitory action of bFGF and TGFbeta1 on AT2 binding sites but not on AT2 mRNA levels. None of these factors modified AT2 mRNA half-life. The potential effects of these factors on transcription of the AT2 gene were measured by means of nuclear run-on assays. IGF-1 increased the rate of transcription by about 2.5-fold, whereas bFGF and TGFbeta1 reduced it by 90 and 80%, respectively. In contrast, AngII did not modify either the basal or IGF-1-stimulated transcription rate. Finally, AngII alone or together with IGF-1, but not IGF-1 alone, increased the attachment of AT2 mRNA to polysomal fractions. The present findings demonstrate that the main mechanism by which AngII regulates the AT2 receptor is by increasing the rate of AT2 mRNA translation, whereas the stimulatory (IGF-1) or inhibitory (bFGF and TGFbeta1) effects of these growth factors on AT2 expression are exerted at the transcriptional level.

Activation of casein kinase II in ML-1 human myeloblastic leukemia cells requires IGF-1 and transferrin.

Casein kinase II (CK II), a key enzyme involved in the regulation of cell growth, has been variously reported to be activated by diverse mitogens, including insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF). Activation of the enzyme is generally carried out in the presence of serum, and we examined the question whether serum components participate in the activation process. We demonstrated previously that ML-1 cells require IGF-1 plus transferrin (TF) for growth and transforming growth factor beta or tumor necrosis factor alpha plus TF for differentiation. We now found that CK II is activated only when the cells are exposed to both IGF-1 and TF or when TF is replaced in this combination with relatively high levels of iron salts. Induction of differentiation with TGF-beta and TF did not result in CK II activation. These results show that CK II activation in ML-1 cells requires the application of both components of the growth signal, IGF-1 and TF, demonstrating that the growth factor alone is incapable of enhancing the activity of the enzyme.