Protein Kinase C

Publication Title: 
Journal of Cellular Biochemistry

Tumor-promoting phorbol esters, like growth factors, elicit pleiotropic responses involving biochemical pathways that lead to different biological responses. Genetic variant cell lines that are resistant to mitogenic, differentiation, or transformation responses to tumor promoters have been valuable tools for understanding the molecular bases of these responses.

Author(s): 
Colburn, N. H.
Smith, B. M.
Publication Title: 
Cell

Both poikilotherms and homeotherms live longer at lower body temperatures, highlighting a general role of temperature reduction in lifespan extension. However, the underlying mechanisms remain unclear. One prominent model is that cold temperatures reduce the rate of chemical reactions, thereby slowing the rate of aging. This view suggests that cold-dependent lifespan extension is simply a passive thermodynamic process. Here, we challenge this view in C. elegans by showing that genetic programs actively promote longevity at cold temperatures.

Author(s): 
Xiao, Rui
Zhang, Bi
Dong, Yongming
Gong, Jianke
Xu, Tao
Liu, Jianfeng
Xu, X. Z. Shawn
Publication Title: 
Molecular Psychiatry

Bipolar disorder (BD) is a chronic psychiatric disorder of public health importance affecting >1% of the Swedish population. Despite progress, patients still suffer from chronic mood switches with potential severe consequences. Thus, early detection, diagnosis and initiation of correct treatment are critical.

Author(s): 
Hayashi, A.
Le Gal, K.
Sˆdersten, K.
Vizlin-Hodzic, D.
≈gren, H.
Funa, K.
Publication Title: 
Circulation Research

The premise that oxidative stress, among several other factors, plays an important role in atherogenesis implies that the development and progression of atherosclerosis can be inhibited by antioxidants. In this minireview we discuss several mechanisms by which the antioxidants ascorbate (vitamin C) and alpha-tocopherol (vitamin E) may protect against atherosclerosis. These mechanisms include inhibition of LDL oxidation and inhibition of leukocyte adhesion to the endothelium and vascular endothelial dysfunction.

Author(s): 
Carr, A. C.
Zhu, B. Z.
Frei, B.
Publication Title: 
The Journal of Nutrition

Atherosclerosis is the leading cause of morbidity and mortality in Westernized populations. The monocyte is a crucial cell in the genesis of the atherosclerotic lesion and is present during all stages of atherosclerosis. alpha-Tocopherol (AT) is the most active component of the vitamin E family and is the principal and most potent lipid-soluble antioxidant in plasma and LDL.

Author(s): 
Jialal, I.
Devaraj, S.
Kaul, N.
Publication Title: 
Molecular Psychiatry

Preliminary clinical data indicate that omega-3 fatty acids may be effective mood stabilizers for patients with bipolar disorder. Both lithium and valproic acid are known to inhibit protein kinase C (PKC) activity after subchronic administration in cell culture and in vivo. The current study was undertaken to determine the effects of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on protein kinase C phosphotransferase activity in vitro.

Author(s): 
Seung Kim, H. F.
Weeber, E. J.
Sweatt, J. D.
Stoll, A. L.
Marangell, L. B.
Publication Title: 
Diabetes

Diabetes is a major risk factor for premature atherosclerosis, and oxidative stress appears to be an important mechanism. Previously, we showed that diabetic monocytes produce increased superoxide anion (O(2)(-)), and alpha-tocopherol (AT) supplementation decreases this. The aim of this study was to elucidate the mechanism(s) of O(2)(-) release and inhibition by AT under hyperglycemic (HG) conditions in monocytes.

Author(s): 
Venugopal, Senthil Kumar
Devaraj, Sridevi
Yang, Teddy
Jialal, Ishwarlal
Publication Title: 
Diabetes

Diabetes confers an increased propensity to atherosclerosis. Inflammation is pivotal in atherogenesis, and diabetes is a proinflammatory state. Interleukin (IL)-6, in addition to inducing the acute-phase response, contributes to insulin resistance. Monocytes from type 2 diabetic patients secrete increased IL-6. The aim of this study was to examine molecular mechanisms for increased IL-6 release from monocytes under hyperglycemia. Monocytic cells (THP-1) were cultured in the presence of 5.5 mmol/l (normal) or 15 mmol/l (high) glucose and mannitol.

Author(s): 
Devaraj, Sridevi
Venugopal, Senthil K.
Singh, Uma
Jialal, Ishwarlal
Publication Title: 
The Journal of Biological Chemistry

The roles of MEK, ERK, the epsilon and alpha isoforms of protein kinase C (PKC), and caveolin-1 in regulating collagen expression were studied in normal lung fibroblasts. Knocking down caveolin-1 gave particularly striking results. A 70% decrease caused a 5-fold increase in MEK/ERK activation and collagen expression. The combined data reveal a branched signaling pathway. In its central portion MEK activates ERK, leading to increased collagen expression. Two branches converge on MEK/ERK. In one, increased PKCepsilon leads to MEK/ERK activation.

Author(s): 
Tourkina, Elena
Gooz, Pal
Pannu, Jaspreet
Bonner, Michael
Scholz, Dimitri
Hacker, Sharon
Silver, Richard M.
Trojanowska, Maria
Hoffman, Stanley
Publication Title: 
American Journal of Physiology. Endocrinology and Metabolism

Previously, IL-1beta secretion from Type 2 diabetic patients has been shown to be increased compared with controls. In this study, we aimed to delineate the mechanism of IL-1beta induction under high-glucose (HG) conditions in human monocytes. THP-1 cells cultured in normal glucose were treated with increasing concentrations of d-glucose (10-25 mM) for 6-72 h. IL-1beta and IL-1 receptor antagonist levels were measured by ELISA and Western blots, whereas mRNA was quantitated by RT-PCR.

Author(s): 
Dasu, Mohan R.
Devaraj, Sridevi
Jialal, Ishwarlal

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