Role of Extracellular Signal-regulated Kinase 5 in Adipocyte Signaling

Zhu, Hong; Guariglia, Sara R.; Li, Wenjing; Brancho, Deborah Marie; Wang, Zhao V.; Scherer, Philipp E.; Chow, Chi Wing

doi:10.1074/jbc.m113.506584

Cited by 21 publications

(18 citation statements)

References 91 publications

(102 reference statements)

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“…In addition, the authors showed that CA-MEK5α overexpression could activate ERK5 by inhibiting its SUMOylation ( Shishido et al, 2008 ). Furthermore, in another study, blood glucose concentrations were found to be elevated in adipocyte specific ERK5 deficient mice and insulin sensitivity to be attenuated as compared with wild-type mice ( Zhu et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study, we reported diabetic stimuli reduced the ERK5 transcriptional activity through ERK5-SUMOylation in endothelial cells, and that ERK5-SUMOylation was increased in a mouse model of STZ-induced diabetic cardiac dysfunction induced by myocyte apoptosis ( Le et al, 2012 ; Woo et al, 2008 ). Recently, it was reported that high fat diet Adipo-ERK5 deficient mice exhibited increased body weight as compared with control littermates, thus suggesting ERK5 plays a protective role of ERK5 in metabolic disease ( Shishido et al, 2008 ; Zhu et al, 2014 ). However, the role played by ERK5 in the diabetic pancreas has not been addressed.…”

Section: Introductionmentioning

confidence: 99%

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CHOP Deficiency Ameliorates ERK5 Inhibition-Mediated Exacerbation of Streptozotocin-Induced Hyperglycemia and Pancreatic β-Cell Apoptosis

Nam

Han

Lim

et al. 2017

Molecules and Cells

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Streptozotocin (STZ)-induced murine models of type 1 diabetes have been used to examine ER stress during pancreatic β-cell apoptosis, as this ER stress plays important roles in the pathogenesis and development of the disease. However, the mechanisms linking type 1 diabetes to the ER stress-modulating anti-diabetic signaling pathway remain to be addressed, though it was recently established that ERK5 (Extracellular-signal-regulated kinase 5) contributes to the pathogeneses of diabetic complications. This study was undertaken to explore the mechanism whereby ERK5 inhibition instigates pancreatic β-cell apoptosis via an ER stress-dependent signaling pathway. STZ-induced diabetic WT and CHOP deficient mice were i.p. injected every 2 days for 6 days under BIX02189 (a specific ERK5 inhibitor) treatment in order to evaluate the role of ERK5. Hyperglycemia was exacerbated by co-treating C57BL/6J mice with STZ and BIX02189 as compared with mice administered with STZ alone. In addition, immunoblotting data revealed that ERK5 inhibition activated the unfolded protein response pathway accompanying apoptotic events, such as, PARP-1 and caspase-3 cleavage. Interestingly, ERK5 inhibition-induced exacerbation of pancreatic β-cell apoptosis was inhibited in CHOP deficient mice. Moreover, transduction of adenovirus encoding an active mutant form of MEK5α, an upstream kinase of ERK5, inhibited STZ-induced unfolded protein responses and β-cell apoptosis. These results suggest that ERK5 protects against STZ-induced pancreatic β-cell apoptosis and hyperglycemia by interrupting the ER stress-mediated apoptotic pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CHOP Deficiency Ameliorates ERK5 Inhibition-Mediated Exacerbation of Streptozotocin-Induced Hyperglycemia and Pancreatic β-Cell Apoptosis

Nam

Han

Lim

et al. 2017

Molecules and Cells

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“…Previous studies showed that these signaling pathways are related to adipocyte differentiation and fat metabolism. MAPK signaling pathway involves four pathways, including ERK1/2, JNK, p38 MAPK and ERK5/BMK1, which have played an important role in adipopexis [52][53][54][55]. The Wnt signaling pathway is involved in the fate determination of the fat cell, adipogenic differentiation and lipometabolism [56,57].…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: An integrated analysis of microRNAs involved in fat deposition in different pig breeds

Zhang¹,

Huang²,

Guo³

et al. 2017

Oncotarget

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The domestic pig, an important species in the animal production industry, is also a model system for studying fat deposition and fat-associated diseases in humans. In order to investigate the genetic relationships of the miRNAs that may regulate fat deposition, we performed a genome-wide analysis of miRNAs derived from subcutaneous adipose tissue of Laiwu and Large White pig using RNA-seq. A total of 26,486,906 reads were obtained. Further analysis indicated that 39 known miRNAs and 56 novel miRNAs had significantly differential expression between the two breeds of pigs. Gene Ontology and KEGG pathway analysis revealed that the predicted targets of these differentially expressed miRNAs were involved in several fat-associated pathways, such as the PPAR, MAPK and Wnt signaling pathways. In addition, we found that three miRNAs, ssc-miR-133a-3p, ssc-miR-486 and ssc-miR-1, had an impact on the development of porcine subcutaneous fat through the PPAR signaling pathway. This study provides clues to understand the potential mechanisms of adipogenesis and fat deposition between two different pig breeds. Furthermore, these results may also contribute to the research involving human obesity.

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“…ERK5 has an opposing action to calcineurin on NFATc4-mediated gene transcription which changes the levels of adipokines expression. The deletion of ERK5 increased adiposity with dysregulation in adipokines secretion, leptin resistance, and impaired glucose handling [116]. It has been identified that above effect of ERK5 in diabetic nephropathy is mediated by TGFβ1 induced phosphorylation of MEK5 without involvement of the MAP3K Ras [117].…”

Section: Role Of Erks In Glucose Metabolism and Insulin Resistancementioning

confidence: 99%

Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance

2016

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Obesity induced low-grade inflammation (metaflammation) impairs insulin receptor signaling (IRS). This has been implicated in the development of insulin resistance. Insulin signaling in the target tissues is mediated by stress kinases such as p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase (JNK), inhibitor of NF-kB kinase complex beta (IKKβ), AMP activated protein kinase (AMPK), protein kinase C (PKC), Rho associated coiled-coil containing protein kinase (ROCK) and RNA-activated protein kinase (PKR), etc. Most of these kinases phosphorylate several key regulators in glucose homeostasis. The phosphorylation of serine residues in the insulin receptor (IR) and IRS-1 molecule results in diminished enzymatic activity in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. This has been one of the key mechanisms observed in the tissues that are implicated in insulin resistance especially in Type II Diabetes Mellitus (T2-DM). Identifying the specific protein kinases involved in obesity induced chronic inflammation may help in developing the targeted drug therapies to minimize the insulin resistance. This review is focused on the protein kinases involved in the inflammatory cascade and molecular mechanisms and their downstream targets with special reference to obesity induced T2-DM.

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Role of Extracellular Signal-regulated Kinase 5 in Adipocyte Signaling

Cited by 21 publications

References 91 publications

CHOP Deficiency Ameliorates ERK5 Inhibition-Mediated Exacerbation of Streptozotocin-Induced Hyperglycemia and Pancreatic β-Cell Apoptosis

CHOP Deficiency Ameliorates ERK5 Inhibition-Mediated Exacerbation of Streptozotocin-Induced Hyperglycemia and Pancreatic β-Cell Apoptosis

WITHDRAWN: An integrated analysis of microRNAs involved in fat deposition in different pig breeds

Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance

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