cDNA cloning and functional analysis of a truncated STAT5a protein from autonomously growing FDCP-1 cells

Bittorf, Thomas; Sasse, Tilo; Wright, Michael; Jaster, Robert; Otte, Livia; Schneider‐Mergener, Jens; Brock, Josef

doi:10.1016/s0898-6568(00)00112-1

Cited by 12 publications

(6 citation statements)

References 41 publications

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“…Although truncation of the carboxy-terminal domain of STAT5 by a serine protease resulted in generation of a dominant-negative form, [6][7][8][9] additional trimming of the carboxy-terminal domain of STAT5A due to alternative splicing has also been reported. 21 Overexpression of truncated STAT5A (devoid of transactivation and Src homology 2 domains) in interleukin 3 (IL-3)-dependent FDCP-1 cells increased DNA-binding activity of endogenous (wild-type) STAT5, enhanced proliferation, and prevented apoptosis after deprivation of IL-3. 21 Our finding that cleavage of both STATs by calpain led to generation of multiple bands, some of which had molecular weights similar to those in earlier reports, indicates that the effects of truncation of STATs by calpain are complex.…”

Section: Resultsmentioning

confidence: 99%

“…21 Overexpression of truncated STAT5A (devoid of transactivation and Src homology 2 domains) in interleukin 3 (IL-3)-dependent FDCP-1 cells increased DNA-binding activity of endogenous (wild-type) STAT5, enhanced proliferation, and prevented apoptosis after deprivation of IL-3. 21 Our finding that cleavage of both STATs by calpain led to generation of multiple bands, some of which had molecular weights similar to those in earlier reports, indicates that the effects of truncation of STATs by calpain are complex.…”

Section: Resultsmentioning

confidence: 99%

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Calpain is a signal transducer and activator of transcription (STAT) 3 and STAT5 protease

Oda

Wakao

Fujita

2002

Blood

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Calpain is a signal transducer and activator of transcription (STAT) 3 and STAT5 protease

Oda

Wakao

Fujita

2002

Blood

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“…Several studies suggest that the EPO neuroprotective signaling pathways have some similarities to the pathways in erythropoiesis, including activations of Janus-tyrosine kinase 2 (Jak2) (Bittorf et al, 1997;Kawakami et al, 2001), signal transducers and activators of transcription (STATs) (Bittorf et al, 2000;Damen et al, 1995) and of nuclear factor kappaB (NFkB) (Figueroa et al, 2002;Matsushita et al, 2003). When the EPO molecule binds to the EPOR, a dimerization of the receptor occurs with subsequent autophosphorylation of Jak2 and receptor activation.…”

Section: Discussionmentioning

confidence: 99%

Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen–glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures

Montero

Poulsen

Noraberg

et al. 2007

Experimental Neurology

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In addition to its well-known hematopoietic effects, erythropoietin (EPO) also has neuroprotective properties. However, hematopoietic side effects are unwanted for neuroprotection, underlining the need for EPO-like compounds with selective neuroprotective actions. One such compound, devoid of hematopoietic bioactivity, is the chemically modified, EPO-derivative carbamylerythropoietin (CEPO). For comparison of the neuroprotective effects of CEPO and EPO, we subjected organotypic hippocampal slice cultures to oxygen-glucose deprivation (OGD) or N-methyl-D-aspartate (NMDA) excitotoxicity. Hippocampal slice cultures were pretreated for 24 h with 100 IU/ml EPO (= 26 nM) or 26 nM CEPO before OGD or NMDA lesioning. Exposure to EPO and CEPO continued during OGD and for the next 24 h until histology, as well as during the 24 h exposure to NMDA. Neuronal cell death was quantified by cellular uptake of propidium iodide (PI), recorded before the start of OGD and NMDA exposure and 24 h after. In cultures exposed to OGD or NMDA, CEPO reduced PI uptake by 49 ± 3 or 35 ± 8%, respectively, compared to lesion-only controls. EPO reduced PI uptake by 33 ± 5 and 15 ± 8%, respectively, in the OGD and NMDA exposed cultures. To elucidate a possible mechanism involved in EPO and CEPO neuroprotection against OGD, the integrity of α-II-spectrin cytoskeletal protein was studied. Both EPO and CEPO significantly reduced formation of spectrin cleavage products in the OGD model. We conclude that CEPO is at least as efficient neuroprotectant as EPO when excitotoxicity is modeled in mouse hippocampal slice cultures.

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“…In erythroleukemic cell lines, EPO-dependent cell survival is accompanied by sustained STAT5 DNA-binding activity. Stable expression of the truncated STAT5a has been shown to enhance STAT5-DNA binding activity and reduce the induction of apoptosis (Bittorf, et al, 2000). In contrast, induction of apoptosis can be observed in cells that lack STAT5 (STAT5a −/− /5b −/ ) function (Socolovsky, et al, 2001).…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Erythropoietin and Oxidative Stress

Maiese

Chong

Hou

et al. 2008

CNR

110

113

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Unmitigated oxidative stress can lead to diminished cellular longevity, accelerated aging, and accumulated toxic effects for an organism. Current investigations further suggest the significant disadvantages that can occur with cellular oxidative stress that can lead to clinical disability in a number of disorders, such as myocardial infarction, dementia, stroke, and diabetes. New therapeutic strategies are therefore sought that can be directed toward ameliorating the toxic effects of oxidative stress. Here we discuss the exciting potential of the growth factor and cytokine erythropoietin for the treatment of diseases such as cardiac ischemia, vascular injury, neurodegeneration, and diabetes through the modulation of cellular oxidative stress. Erythropoietin controls a variety of signal transduction pathways during oxidative stress that can involve Janus-tyrosine kinase 2, protein kinase B, signal transducer and activator of transcription pathways, Wnt proteins, mammalian forkhead transcription factors, caspases, and nuclear factor κB. Yet, the biological effects of erythropoietin may not always be beneficial and may be poor tolerated in a number of clinical scenarios, necessitating further basic and clinical investigations that emphasize the elucidation of the signal transduction pathways controlled by erythropoietin to direct both successful and safe clinical care. KeywordsAlzheimer's disease; Akt; angiogenesis; apoptosis; cancer; cardiac; caspases; diabetes; endothelial; erythropoietin; forkhead; FoxO; GSK-3β; inflammation; mitochondria; NF-κB; renal; STATs; Wnt OXIDATIVE STRESSInitial work in pathways that can lead to oxidative stress by early investigators observed that increased metabolic rates could be detrimental to animals in an elevated oxygen environment. More current studies point to the potential aging mechanisms and accumulated toxic effects for an organism that are tied to oxidative stress (Maiese, et al., 2008a NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript in organisms, or at least the rate of oxygen consumption in organisms, has intrigued several investigators. Pearl proposed that increased exposure to oxygen through an increased metabolic rate could lead to a shortened life span (Pearl, 1928). Subsequent work by multiple investigators has furthered this hypothesis by demonstrating that increased metabolic rates could be detrimental to animals in an elevated oxygen environment . When one moves to more current work, oxygen free radicals and mitochondrial DNA mutations have become associated with oxidative stress injury, aging mechanisms, and accumulated toxicity for an organism (Yui and Matsuura, 2006).Oxygen free radicals can be generated in elevated quantities during the reduction of oxygen and subsequently lead to cell injury and apoptosis. Oxidative stress occurs as a result of the development of reactive oxygen species that consist of oxygen free radicals and other chemical entities. These agents can involve superoxide free radicals, hydrogen peroxide, sin...

show abstract

cDNA cloning and functional analysis of a truncated STAT5a protein from autonomously growing FDCP-1 cells

Cited by 12 publications

References 41 publications

Calpain is a signal transducer and activator of transcription (STAT) 3 and STAT5 protease

Calpain is a signal transducer and activator of transcription (STAT) 3 and STAT5 protease

Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen–glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures

Erythropoietin and Oxidative Stress

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