Article thumbnail

Numb Protects Renal Proximal Tubular Cells from Puromycin Aminonucleoside-Induced Apoptosis through Inhibiting Notch Signaling Pathway

By Xuebing Ding, Fengxin Zhu, Tang Li, Qiugen Zhou, Fan Fan Hou and Jing Nie

Abstract

Numb was originally discovered as an intrinsic cell fate determinant in Drosophila by antagonizing Notch signaling. The present study is to characterize the role of Numb in oxidative stress-induced apoptosis of renal proximal tubular cells. Exposure of NRK52E cells to puromycin aminonucleoside (PA) resulted in caspase 3-dependent apoptosis. Numb expression was downregulated by PA in a time- and dose-dependent manner. Knocking down endogenous Numb by siRNA sensitized NRK52E cells to PA-induced apoptosis, whereas overexpressing Numb protected NRK52E cells from PA-induced apoptosis. Moreover, PA activated Notch signaling in a time- and dose-dependent manner as indicated by increased expression of the intracellular domain of Notch and Hes-1. Notch signaling inhibitor DAPT significantly attenuated Numb siRNA-augmented apoptosis. On the other hand, overexpression of intracellular domain of Notch1 could reverse the protective effect of Numb on PA-induced apoptosis. Taken together, our data demonstrated that, in renal proximal tubular cells, Numb functions as a protective molecule on PA-induced apoptosis through antagonizing Notch signaling activity

Topics: Research Paper
Publisher: Ivyspring International Publisher
OAI identifier: oai:pubmedcentral.nih.gov:3065739
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. (2002). Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med.
  2. (2005). Acute renal failure. Lancet.
  3. (2008). Adrenomedullin protects against oxidative stress-induced podocyte injury as an endogenous antioxidant. Nephrol Dial Transplant.
  4. (2002). Apoptosis and inflammation in renal reperfusion injury. Transplantation.
  5. (1996). Asymmetric localization of a mammalian numb homolog during mouse cortical neurogenesis. Neuron.
  6. (1998). Caspases: the proteases of the apoptotic pathway. Oncogene.
  7. (1999). Characterization of four mammalian numb protein isoforms. Identification of cytoplasmic and membrane-associated variants of the phosphotyrosine binding domain. J Biol Chem.
  8. (2008). Characterization of Numb expression in astrocytomas. Neuropathology.
  9. (1996). Control of daughter cell fates during asymmetric division: interaction of Numb
  10. (1999). Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage.
  11. (2001). Dynamics of notch expression during murine prostate development and tumorigenesis. Cancer Res.
  12. (2005). Effect of a novel free radical scavenger, edaravone, on puromycin aminonucleoside induced nephrosis in rats. Pediatr Nephrol.
  13. (1996). Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles. J Exp Med.
  14. (1998). Identification of gene family of caspases in rat kidney and altered expression in ischemia-reperfusion injury.
  15. (1992). IL-1 alpha stimulated TNF alpha production by cultured human proximal tubular epithelial cells. Kidney Int.
  16. (2004). Increased oxidative stress and apoptosis in acute puromycin aminonucleoside nephrosis. Int J Exp Pathol.
  17. (1999). Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation. J Clin Invest.
  18. (1996). Mammalian NUMB is an evolutionarily conserved signaling adapter protein that specifies cell fate. Curr Biol.
  19. (2003). Mammalian numb proteins promote Notch1 receptor ubiquitination and degradation of the Notch1 intracellular domain.
  20. (2009). MMP9 and SCF protect from apoptosis in acute kidney injury. J Am Soc Nephrol.
  21. (2003). Notch signaling in hematopoiesis. Semin Cell Dev Biol.
  22. (2001). Notch signaling induces cell cycle arrest in small cell lung cancer cells. Cancer Res.
  23. (2001). Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. Embo J.
  24. (1996). Numb antagonizes Notch signaling to specify sibling neuron cell fates.
  25. (2002). Numb isoforms containing a short PTB domain promote neurotrophic factor-induced differentiation and neurotrophic factor withdrawal-induced death of PC12 Cells.
  26. (1999). NUMB localizes in the basal cortex of mitotic avian neuroepithelial cells and modulates neuronal differentiation by binding to NOTCH-1. Neuron.
  27. (2003). Prevention of renal damage by alpha tocopherol in ischemia and reperfusion models of rats. Urol Res.
  28. (2000). Proapoptotic Fas ligand is expressed by normal kidney tubular epithelium and injured glomeruli. J Am Soc Nephrol.
  29. (2001). Puromycin aminonucleoside induces apoptosis and increases HNE in cultured glomerular epithelial cells(1). Free Radic Biol Med.
  30. (2001). Puromycin aminonucleoside induces glomerular epithelial cell apoptosis. Exp Mol Pathol.
  31. (2003). Role of apoptosis in hypoxic/ischemic damage in the kidney. Semin Nephrol.
  32. (2004). Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury.
  33. (2005). The pathophysiology of acute renal failure. Crit Care Clin.