QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takagi, Y. Articles by Nagase, F. Search for Related Content PubMed PubMed Citation Articles by Takagi, Y. Articles by Nagase, F.

Phorbol 12-Myristate 13-Acetate Protects Jurkat Cells from Methylglyoxal-Induced Apoptosis by Preventing c-Jun N-Terminal Kinase-Mediated Leakage of Cytochrome c in an Extracellular Signal-Regulated Kinase-Dependent Manner

Department of Medical Technology, Nagoya University School of Health Sciences, Aichi, Japan (Y.T., J.D., X.-Y.M., F.N.); and Department of Immunology, Nagoya University Graduate School of Medicine, Aichi, Japan (X.-Y.M., I.N.)

Methylglyoxal (MG) is an endogenous metabolite that increases in the blood and tissues of diabetic patients and is believed to be linked to the development of chronic complications of diabetes. We showed previously that Jurkat cells treated with MG rapidly undergo apoptosis via c-Jun N-terminal kinase (JNK) activation. In this study, we examined whether phorbol 12-myristate 13-acetate (PMA) can prevent MG-induced apoptosis in Jurkat cells. The results showed the following: 1) PMA can prevent MG-induced apoptosis; 2) triggering of this antiapoptotic signal depends on the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) pathway; 3) PMA inhibits MG-induced activation of caspase-3 and caspase-9, release of cytochrome c, and decline of mitochondrial membrane potential, but it does not affect MG-induced JNK activation; 4) the ERK pathway modulates outer mitochondrial membrane permeability and regulates the mitochondrial death machinery; and 5) activated ERK prevents JNK-induced leakage of cytochrome c from isolated mitochondria. Taken together, these results suggest that PMA-induced ERK activation can protect Jurkat cells from methylglyoxal-induced apoptosis and that activated ERK exerts its antiapoptotic effects on mitochondria by inhibiting activated JNK-induced permeabilization of the outer mitochondrial membrane.

Address correspondence to: Dr. Fumihiko Nagase, Department of Medical Technology, Nagoya University School of Health Sciences, 1-20 Daikominami-1-chome, Higashi-ku, Nagoya 461-8673, Japan. E-mail: nagase{at}met.nagoya-u.ac.jp

This article has been cited by other articles:

				B. Menon, M. Singh, R. S. Ross, J. N. Johnson, and K. Singh {beta}-Adrenergic receptor-stimulated apoptosis in adult cardiac myocytes involves MMP-2-mediated disruption of {beta}1 integrin signaling and mitochondrial pathway Am J Physiol Cell Physiol, January 1, 2006; 290(1): C254 - C261. [Abstract] [Full Text] [PDF]