Regulation of CD95 (Fas) expression and Fas-mediated apoptotic signaling in HLE B-3 cells by 4-hydroxynonenal

Jie Li, Rajendra Sharma, Brad Patrick, Abha Sharma, Prince V S Jeyabal, Prasada M R V Reddy, Manjit K. Saini, Seema Dwivedi, Shaheen Dhanani, Naseem Ansari, Piotr Zimniak, Sanjay Awasthi, Yogesh C. Awasthi

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Abstract

The Fas (apo/CD95) receptor which belongs to the TNF-α family is a transmembrane protein involved in the signaling for apoptosis through the extrinsic pathway. During this study, we have examined a correlation between intracellular levels of 4-HNE and expression of Fas in human lens epithelial (HLE B-3) cells. Our results show that in HLE B-3 cells, Fas is induced by 4-HNE in a concentration- and time-dependent manner, and it is accompanied by the activation of JNK, caspase 3, and the onset of apoptosis. Fas induction and activation of JNK are also observed in various tissues of mGsta4 null mice which have elevated levels of 4-HNE. Conversely, when 4-HNE is depleted in HLE B-3 cells by a transient transfection with hGSTA4, Fas expression is suppressed. However, upon the cessation of HGSTA4 expression in these transiently transfected cells, Fas and 4-HNE return to their basal levels. Fas-deficient transformed HLE B-3 cells stably transfected with hGSTA4 show remarkable resistance to apoptosis. Also, the wild-type HLE B-3 cells in which Fas is partially depleted by siRNA acquire resistance to 4-HNE-induced apoptosis, suggesting an at least partial role of Fas in 4-HNE-induced apoptosis in HLE B-3 cells. We also demonstrate that during 4-HNE-induced apoptosis of HLE B-3 cells, Daxx is induced and it binds to Fas. Together, these results show an important role of 4-HNE in regulation of the expression and functions of Fas.

Original languageEnglish (US)
Pages (from-to)12253-12264
Number of pages12
JournalBiochemistry
Volume45
Issue number40
DOIs
StatePublished - Oct 10 2006

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Apoptosis
Chemical activation
Caspase 3
Small Interfering RNA
4-hydroxy-2-nonenal
Lenses
Tissue
Transfection
Proteins
leukotriene-C4 synthase

ASJC Scopus subject areas

  • Biochemistry

Cite this

Li, J., Sharma, R., Patrick, B., Sharma, A., Jeyabal, P. V. S., Reddy, P. M. R. V., ... Awasthi, Y. C. (2006). Regulation of CD95 (Fas) expression and Fas-mediated apoptotic signaling in HLE B-3 cells by 4-hydroxynonenal. Biochemistry, 45(40), 12253-12264. https://doi.org/10.1021/bi060780+

Regulation of CD95 (Fas) expression and Fas-mediated apoptotic signaling in HLE B-3 cells by 4-hydroxynonenal. / Li, Jie; Sharma, Rajendra; Patrick, Brad; Sharma, Abha; Jeyabal, Prince V S; Reddy, Prasada M R V; Saini, Manjit K.; Dwivedi, Seema; Dhanani, Shaheen; Ansari, Naseem; Zimniak, Piotr; Awasthi, Sanjay; Awasthi, Yogesh C.

In: Biochemistry, Vol. 45, No. 40, 10.10.2006, p. 12253-12264.

Research output: Contribution to journalArticle

Li, J, Sharma, R, Patrick, B, Sharma, A, Jeyabal, PVS, Reddy, PMRV, Saini, MK, Dwivedi, S, Dhanani, S, Ansari, N, Zimniak, P, Awasthi, S & Awasthi, YC 2006, 'Regulation of CD95 (Fas) expression and Fas-mediated apoptotic signaling in HLE B-3 cells by 4-hydroxynonenal', Biochemistry, vol. 45, no. 40, pp. 12253-12264. https://doi.org/10.1021/bi060780+
Li J, Sharma R, Patrick B, Sharma A, Jeyabal PVS, Reddy PMRV et al. Regulation of CD95 (Fas) expression and Fas-mediated apoptotic signaling in HLE B-3 cells by 4-hydroxynonenal. Biochemistry. 2006 Oct 10;45(40):12253-12264. https://doi.org/10.1021/bi060780+
Li, Jie ; Sharma, Rajendra ; Patrick, Brad ; Sharma, Abha ; Jeyabal, Prince V S ; Reddy, Prasada M R V ; Saini, Manjit K. ; Dwivedi, Seema ; Dhanani, Shaheen ; Ansari, Naseem ; Zimniak, Piotr ; Awasthi, Sanjay ; Awasthi, Yogesh C. / Regulation of CD95 (Fas) expression and Fas-mediated apoptotic signaling in HLE B-3 cells by 4-hydroxynonenal. In: Biochemistry. 2006 ; Vol. 45, No. 40. pp. 12253-12264.
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abstract = "The Fas (apo/CD95) receptor which belongs to the TNF-α family is a transmembrane protein involved in the signaling for apoptosis through the extrinsic pathway. During this study, we have examined a correlation between intracellular levels of 4-HNE and expression of Fas in human lens epithelial (HLE B-3) cells. Our results show that in HLE B-3 cells, Fas is induced by 4-HNE in a concentration- and time-dependent manner, and it is accompanied by the activation of JNK, caspase 3, and the onset of apoptosis. Fas induction and activation of JNK are also observed in various tissues of mGsta4 null mice which have elevated levels of 4-HNE. Conversely, when 4-HNE is depleted in HLE B-3 cells by a transient transfection with hGSTA4, Fas expression is suppressed. However, upon the cessation of HGSTA4 expression in these transiently transfected cells, Fas and 4-HNE return to their basal levels. Fas-deficient transformed HLE B-3 cells stably transfected with hGSTA4 show remarkable resistance to apoptosis. Also, the wild-type HLE B-3 cells in which Fas is partially depleted by siRNA acquire resistance to 4-HNE-induced apoptosis, suggesting an at least partial role of Fas in 4-HNE-induced apoptosis in HLE B-3 cells. We also demonstrate that during 4-HNE-induced apoptosis of HLE B-3 cells, Daxx is induced and it binds to Fas. Together, these results show an important role of 4-HNE in regulation of the expression and functions of Fas.",
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AU - Reddy, Prasada M R V

AU - Saini, Manjit K.

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AU - Dhanani, Shaheen

AU - Ansari, Naseem

AU - Zimniak, Piotr

AU - Awasthi, Sanjay

AU - Awasthi, Yogesh C.

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