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We tested the hypothesis that AMP-activated protein kinase (AMPK), an energy sensor, regulates diabetes-induced renal hypertrophy. In kidney glomerular epithelial cells, high glucose (30 mM), but not equimolar mannitol, stimulated de novo protein synthesis and induced hypertrophy in association with increased phosphorylation of eukaryotic initiation factor(More)
The proliferation and migration of arterial smooth muscle cells (SMCs) are key events in the vascular restenosis that frequently follows angioplasty. Furthermore, SMC migration and neointimal hyperplasia are promoted by degradation of the extracellular matrix by matrix metalloproteinases (MMPs). Because we demonstrated previously that the proinflammatory(More)
Chemotactic factors known as chemokines play an important role in the pathogenesis of multiple sclerosis (MS). Transgenic expression of TNFalpha in the central nervous system (CNS) leads to the development of a demyelinating phenotype (TNFalpha-induced demyelination; TID) that is highly reminiscent of MS. Little is known about the role of chemokines in TID(More)
Mesangioproliferative glomerulonephritis is associated with overactive PDGF receptor signal transduction. We show that the phytoalexin resveratrol dose dependently inhibits PDGF-induced DNA synthesis in mesangial cells with an IC(50) of 10 microM without inducing apoptosis. Remarkably, the increased SIRT1 deacetylase activity induced by resveratrol was not(More)
The mechanism by which bone morphogenetic protein-2 (BMP-2) induces osteoblast differentiation is not precisely known. We investigated the involvement of the phosphatidylinositol (PI) 3-kinase/Akt signal transduction pathway in modulation of this process. BMP-2 stimulated PI 3-kinase activity in osteogenic cells. Inhibition of PI 3-kinase activity with the(More)
Platelet-derived growth factor BB (PDGF) and PDGF receptor-beta (PDGFR) play critical roles in mesangial cell proliferation during embryonic development and in mesangioproliferative glomerulonephritis. We have shown previously that phosphatidylinositol (PI) 3 kinase/Akt and Erk1/2 mitogen-activated protein kinase (MAPK) contribute to PDGF-dependent(More)
Reactive oxygen species (ROS) contribute to many glomerular diseases by targeting mesangial cells. ROS have been shown to regulate expression of many antioxidant enzymes including catalase. The mechanism by which the expression of catalase protein is regulated by ROS is not precisely known. Here we report that increased intracellular ROS level by hydrogen(More)
The tumor suppressor gene PTEN (phosphatase and tensin homologue deleted on chromosome 10) antagonizes the pro-survival signaling of Akt and promotes cell death. Previously, we demonstrated that IL-18 induced apoptosis in human cardiac microvascular endothelial cells (HCMEC). Here we have investigated the role of PTEN in this response. Our results(More)
Nuclear factor-erythroid 2-related factor 2 (Nrf2/NFE2L2), a redox-sensitive transcription factor plays a critical role in adaptation to cellular stress and affords cellular defense by initiating transcription of antioxidative and detoxification genes. While a protein can be regulated at multiple levels, control of Nrf2 has been largely studied at(More)
Ethanol (ETOH) can cause apoptotic death of neurons by depleting GSH with an associated increase in oxidative stress. The current study illustrates a means to overcome this ETOH-induced neurotoxicity by enhancing GSH through boosting Nrf2, a transcription factor that controls GSH homeostasis. ETOH treatment caused a significant increase in Nrf2 protein,(More)