Integrin-associated Lyn Kinase Promotes Cell Survival by Suppressing Acid Sphingomyelinase Activity

Chudakova, Daria A.; Zeidan, Youssef H.; Wheeler, Brian W.; Yu, Jin; Novgorodov, Sergei A.; Kindy, Mark S.; Hannun, Yusuf A.; Gudz, Tatyana I.

doi:10.1074/jbc.m803301200

Cited by 40 publications

(64 citation statements)

References 62 publications

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“…Consistent with these data, the extent of brain tissue damage was decreased in mice lacking aSMase (Yu et al, 2000). In a recent study, severe cerebral IR induced SM hydrolysis and increased ceramide and sphingosine in the ischemic brain (Chudakova et al, 2008). Similarly, chronic cerebral ischemia caused ceramide accumulation due to activation of SM degradation accompanied by reduced ceramide utilization via glucosylceramide synthase (Ohtani et al, 2004).…”

Section: Cerebral Ischemiasupporting

confidence: 71%

“…It has been demonstrated that generation of C 18:0 -ceramide, and not C 16:0 -ceramide repressed human telomerase reverse transcriptase promoter in lung carcinoma cells (Wooten-Blanks et al, 2007). Activation of aSMase in the salvage pathway brought about a selective accumulation of C 16:0 -ceramide (Chudakova et al, 2008;Kitatani et al, 2006) due to the involvement of ceramide synthase CerS5 localized in mitochondria-associated membranes (Kitatani et al, 2006). In another study, the effects of chronic hypoxia on selected ceramide species were examined in cardiac tissue in a neonatal mouse model (Noureddine et al, 2008).…”

Section: Ceramide Accumulation In Ischemia/reperfusion (Ir)mentioning

confidence: 99%

See 1 more Smart Citation

Mitochondrial Ceramide in Stroke

Gudz¹,

Novgorodov²

2012

Advances in the Preclinical Study of Ischemic Stroke

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Section: Cerebral Ischemiasupporting

confidence: 71%

Section: Ceramide Accumulation In Ischemia/reperfusion (Ir)mentioning

confidence: 99%

Mitochondrial Ceramide in Stroke

Gudz¹,

Novgorodov²

2012

Advances in the Preclinical Study of Ischemic Stroke

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“…One of the most important is α V β 3 56 which is known to act as a trigger for cell survival 57 and this may be important in angiogenesis where endothelial cell survival is critical. It also plays a key role in metastasis where its expression in melanoma is associated with highly metastatic disease 58 .…”

Section: Integrins and Diseasementioning

confidence: 99%

Integrins as therapeutic targets: lessons and opportunities

Cox

Brennan

Moran

2010

Nat Rev Drug Discov

412

350

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“…Recently, it has been shown that a glycosphingolipid, lactosylceramide, regulates ␤1-integrin clustering and endocytosis (59). Integrin-associated Lyn kinase in lipid rafts also plays a critical role in neural cell survival (60). Those examples indicate that the functions of ␤1-integrin are dependent on its endocytosis, especially in bFGF-induced NECs.…”

Section: ␤1-integrin Up-regulation By Growth Factors In Neural Stem Cmentioning

confidence: 99%

Involvement of β1-Integrin Up-regulation in Basic Fibroblast Growth Factor- and Epidermal Growth Factor-induced Proliferation of Mouse Neuroepithelial Cells

Suzuki

Yanagisawa

Yagi

et al. 2010

Journal of Biological Chemistry

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In neural stem cells, basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) promote cell proliferation and self-renewal. In the bFGF-and EGF-responsive neural stem cells, ␤1-integrin also plays important roles in crucial cellular processes, including proliferation, migration, and apoptosis. The cross-talk of the signaling pathways mediated by these growth factors and ␤1-integrin, however, has not been fully elucidated. Here we report a novel molecular mechanism through which bFGF or EGF promotes the proliferation of mouse neuroepithelial cells (NECs). In the NECs, total ␤1-integrin expression levels and proliferation were dose-dependently increased by bFGF but not by EGF. EGF rather than bFGF strongly induced the increase of ␤1-integrin localization on the NEC surface. bFGF-and EGF-induced ␤1-integrin up-regulation and proliferation were inhibited after treatment with a mitogen-activated protein kinase kinase inhibitor, U0126, which indicates the dependence on the mitogen-activated protein kinase pathway. Involvement of ␤1-integrin in bFGF-and EGF-induced proliferation was confirmed by the finding that NEC proliferation and adhesion to fibronectin-coated dishes were inhibited by knockdown of ␤1-integrin using small interfering RNA. On the other hand, apoptosis was induced in NECs treated with RGD peptide, a small ␤1-integrin inhibitor peptide with the Arg-Gly-Asp motif, but it was independent of ␤1-integrin expression levels. Those results suggest that regulation of ␤1-integrin expression/localization is involved in cellular processes, such as proliferation, induced by bFGF and EGF in NECs. The mechanism underlying the proliferation through ␤1-integrin would not be expected to be completely identical, however, for bFGF and EGF.Neural stem cells (NSCs) 3 are defined as undifferentiated neural cells with a high potential for proliferation and the capacity for self-renewal with retention of multipotency (1-4). During development, NSCs have the capability to generate brain-forming cells, such as neurons, astrocytes, and oligodendrocytes. The application of NSCs to cell-based transplantation is a very attractive and promising strategy for regenerative and restorative medicine (5-7).The fate of NSCs (self-renewal, proliferation, differentiation, survival, and death) is regulated by intracellular programs mediated by a number of transcription factors or epigenetic modifications, including DNA methylation, histone modification, and non-coding RNA expression (8 -11). Furthermore, the signaling pathways of various growth factors, the extracellular matrix, and cell adhesion molecules present in specific microenvironments or niche in NSCs are also known to play important roles in maintenance of the stem cell population (12-18). In particular, basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) are primary mitogens to promote proliferation of NSCs through the mitogen-activated protein kinase (MAPK) pathway in vitro (19 -22). The responses of NSCs to those growth factors are thought to ...

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Integrin-associated Lyn Kinase Promotes Cell Survival by Suppressing Acid Sphingomyelinase Activity

Cited by 40 publications

References 62 publications

Mitochondrial Ceramide in Stroke

Mitochondrial Ceramide in Stroke

Integrins as therapeutic targets: lessons and opportunities

Involvement of β1-Integrin Up-regulation in Basic Fibroblast Growth Factor- and Epidermal Growth Factor-induced Proliferation of Mouse Neuroepithelial Cells

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