Premium
Stimulation of autophagy prevents apoptosis of neonatal rat cardiomyocytes exposed to lipopolysaccharide
Author(s) -
HicksonBick Diane L.,
Jones Chad,
Buja L. Maximilian
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a759-a
Subject(s) - autophagy , nitric oxide , lipopolysaccharide , apoptosis , microbiology and biotechnology , stimulation , nitric oxide synthase , mitochondrion , mitochondrial biogenesis , chemistry , programmed cell death , reactive oxygen species , biology , biochemistry , endocrinology
Unlike adult cardiomyocytes, neonatal rat ventricular cardiomyocytes exhibit a protective phenotype towards high levels of lipopolysaccharide (LPS). The physiological basis of this protection is not known. We have previously shown that neonatal cells exposed to LPS exhibit profound changes to their functional mitochondria, these changes include a temporal loss of mitochondria membrane potential and an increased expression of uncoupling protein 3 (UCP 3). Over time these measurements return to pretreatment levels and are not associated with apoptosis induction. We demonstrate that mitochondrial biogenesis is stimulated by LPS treatment. Concomitant with an increase in mitochondrial biogenesis we also observed an increase in the level of autophagy within LPS treated cells. Furthermore, inhibition of autophagy induces apoptosis in the presence of LPS. LPS treatment is associated with an increase in the expression of inducible nitric oxide synthase (iNOS) and increased nitric oxide levels. Our results demonstrate that production of nitric oxide is necessary for the stimulation of autophagy. We propose that the stimulation of autophagy in neonatal cells is a protective phenotype removing mitochondria damaged by LPS, thereby possibly decreasing the production of reactive oxygen species and limiting cell damage. Supported by the Department of Defense # DAMD W81XWH‐04‐02‐0035