Thyrotropin-Releasing Hormone-Stimulated Thyrotropin Expression Involves Islet-Brain-1/c-Jun N-Terminal Kinase Interacting Protein-1

Abe, Hiroshi; Murao, Koji; Imachi, Hitomi; Cao, Wen; Yu, Xiao; Yoshida, Kazuya; Wong, Norman C.W.; Shupnik, Margaret A.; Haefliger, Jacques‐Antoine; Waeber, Gérard; Ishida, Toshihiko

doi:10.1210/en.2004-0635

Cited by 14 publications

(8 citation statements)

References 24 publications

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“…[161718192021] In addition, protein kinase C has been shown to be regulated by iron with possible deleterious effect of excess iron on its function. [212223] Both mechanisms appear to be affected by iron overload and can explain the defective TSH secretion in response to low FT4 in thalassemic patients. The deposition of iron in the pituitary gland and its deleterious effects on pituitary size and functions has been reported in many studies.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years

Soliman

Yafei

Al-Naimi

et al. 2013

Indian J Endocr Metab

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Introduction:Primary hypothyroidism is one of the most frequent complications observed in-patients suffering from thalassemia. We investigated and reviewed the thyroid function in all thalassemic patients attending the Pediatric Endocrine Clinic of Hamad Medical Center, Doha, Qatar during the last 10 years of follow-up.Patients and Methods:A total of 48 patients with ί-thalassemia major between 5 years and 18 years of age. Thyroid dysfunction was defined as follows: Overt hypothyroidism (low Free thyroxine [FT4] and increased thyroid-stimulating hormone [TSH] levels >5 μIU/ml); subclinical hypothyroidism (normal FT4, TSH between 5 μIU/ml and 10 μIU/ml) and central (secondary) hypothyroidism (low FT4 and normal or decreased TSH).Results:A total of 48 patients (22 males and 26 females) completed a 12 year-period of follow-up. During this period, hypothyroidism was diagnosed in 17/48 (35%) of patients. There was no significant difference in the prevalence in males 7/22 (32%) versus females 10/26 (38%). Sixteen of the patients had hypothyroidism after the age of 10 years (94%). The prevalence of overt hypothyroidism had risen from 0% at the age of 7 years to 35% at the age of 18 years. None of the patients had high anti-thyroperoxidase antibody titers. Out of 17 patients, 13 patients with hypothyroidism had normal or low TSH level (not appropriately elevated) indicative of defective hypothalamic pituitary response to low FT4 (central hypothyroidism). Three patients (6.3%) had subclinical hypothyroidism (TSH between 5 uIU/ml and 10 uIU/ml and normal FT4). The general trend of FT4 level showed progressive decrease over the 12 years, whereas, TSH levels did not show a corresponding increase. These data suggested defective hypothalamic pituitary thyroid axis involving both TSH and FT4 sretion in patients with thalassemia major over time. There was a significant negative correlation between serum ferritin and FT4 (r = −0.39, P = 0.007), but no correlation was found between ferritin and TSH.Conclusions:Worsening of thyroid function was observed in 35% of the studied thalassemic patients by the age of 18 years. The lack of proper increase of TSH in response to the low circulating levels of FT4 in 13/17 (76%) of these patients indicates a relatively high incidence of defective pituitary thyrotrophic function in these patients.

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Section: Discussionmentioning

confidence: 99%

Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years

Soliman

Yafei

Al-Naimi

et al. 2013

Indian J Endocr Metab

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“…The supernatants containing protein concentration of 20 lg/ml were used for immunoblotting according to standard procedures. Levels of phosphorylated and total JNK were detected with a 1:1,000 dilution of each specific antiserum (New England Biolabs, Beverly, MA) as described previously [16]. The protein bands were visualized by chemiluminescence.…”

Section: Immunoblotting Of Jnkmentioning

confidence: 99%

c-Jun N-terminal kinases inhibitor suppresses the TNF-α induced MCP-1 expression in human umbilical vein endothelial cells

Ahmed

Murao

Imachi

et al. 2008

Endocr

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Monocyte chemoattractant protein-1 (MCP-1) is a 76-amino-acid chemokine that is considered to be an important chemotactic factor for monocytes. MCP-1 is expressed in the macrophage-rich areas of atherosclerotic lesions. A recent report indicated that MCP-1 expression in human umbilical vein endothelial cells (HUVECs) is induced by the stimulation of tumor necrosis factor (TNF)-alpha via the c-Jun N-terminal kinases (JNK) pathway. In this study, we examined the effects of JNK inhibitor (JNKI-1), on MCP-1 expression. The results of this study indicated that the expression of MCP-1 mRNA and protein were stimulated in the presence of TNF-alpha. TNF-alpha stimulated the phosphrylation of JNK, however, JNKI-1 inhibited the TNF-alpha stimulated MCP-1 secretion and gene expression. As expected, JNKI-1 blocked the stimulatory effect of TNF-alpha on the MCP-1 promoter activity. In conclusion, JNKI-1 partially inhibits the TNF-alpha-induced MCP-1 expression in HUVECs, and therefore JNKI-1 may be of therapeutic value in the treatment of diseases such as atherosclerosis.

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“…Furthermore, in studies of humans, a missense mutation in the coding region of the Jip1 gene that replaces Ser-59 with an Asn residue was found to segregate with type 2 diabetes, demonstrating that the Jip1 gene may contribute to type 2 diabetes (26). This mutation may influence the function of JIP1 (1,3,26). To test this hypothesis, we immunoprecipitated wild-type and Ser-59Asn JIP1 from Rin5F insulinoma cells and examined the amount of associated endogenous JNK and IRS2 by immunoblot analysis.…”

Section: Insulin Regulates the Interaction Of Jip And Irs Scaffold Prmentioning

confidence: 99%

Signal Transduction Cross Talk Mediated by Jun N-Terminal Kinase-Interacting Protein and Insulin Receptor Substrate Scaffold Protein Complexes

Standen

Kennedy

Flavell

et al. 2009

Molecular and Cellular Biology

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Scaffold proteins have been established as important mediators of signal transduction specificity. The insulin receptor substrate (IRS) proteins represent a critical group of scaffold proteins that are required for signal transduction by the insulin receptor, including the activation of phosphatidylinositol 3 kinase. The c-Jun NH 2 -terminal kinase (JNK)-interacting proteins (JIPs) represent a different group of scaffold molecules that are implicated in the regulation of the JNK. These two signaling pathways are functionally linked because JNK can phosphorylate IRS1 on the negative regulatory site Ser-307. Here we demonstrate the physical association of these signaling pathways using a proteomic approach that identified insulin-regulated complexes of JIPs together with IRS scaffold proteins. Studies using mice with JIP scaffold protein defects confirm that the JIP1 and JIP2 proteins are required for normal glucose homeostasis. Together, these observations demonstrate that JIP proteins can influence insulin-stimulated signal transduction mediated by IRS proteins.The c-Jun NH 2 -terminal kinase (JNK)-interacting proteins (JIPs) are implicated in the regulation of the JNK signal transduction pathway (8, 28). The JIP1 and JIP2 proteins are structurally related with similar modular domains (SH3 and PTB) and binding sites for the mixed-lineage protein kinase (MLK) group of mitogen-activated protein kinase (MAPK) kinase kinases, the MAPK kinase MKK7, and JNK (19). These JIP proteins also interact with the microtubule motor protein kinesin, several guanine nucleotide exchange factors, the phosphatase MKP7, Src-related protein kinases, and AKT to form multifunctional protein complexes (19).One potential physiological role of JIP scaffold proteins is the response to metabolic stress, insulin resistance, and diabetes. Several lines of evidence support this hypothesis. First, JIP1 is required for metabolic stress-induced activation of JNK in white adipose tissue (12). Second, MLKs that interact with JIP proteins are implicated as essential components of a signaling pathway that mediates the effects of metabolic stress on JNK activation (13). Third, studies have demonstrated that the human Jip1 gene may contribute to the development of type 2 diabetes, because a Jip1 missense mutation was found to segregate with type 2 diabetes (26). Collectively, these data suggest that JIP proteins play a role in the cellular response to metabolic stress and the regulation of insulin resistance.It is established that the insulin receptor substrate (IRS) group of scaffold proteins plays a central role in insulin signaling (27). Treatment of cells with insulin causes tyrosine phosphorylation of the insulin receptor, the recruitment of IRS proteins to the insulin receptor, and the subsequent tyrosine phosphorylation of IRS proteins on multiple residues that act as docking sites for insulin-regulated signaling molecules, including phosphatidylinositol 3 kinase (27). Negative regulation of IRS proteins is implicated as a mechanism of insulin re...

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Thyrotropin-Releasing Hormone-Stimulated Thyrotropin Expression Involves Islet-Brain-1/c-Jun N-Terminal Kinase Interacting Protein-1

Cited by 14 publications

References 24 publications

Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years

Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years

c-Jun N-terminal kinases inhibitor suppresses the TNF-α induced MCP-1 expression in human umbilical vein endothelial cells

Signal Transduction Cross Talk Mediated by Jun N-Terminal Kinase-Interacting Protein and Insulin Receptor Substrate Scaffold Protein Complexes

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