IRIG: PKC regulation of mitochondria in Science
02/07/2007 09:52
Protein kinase C
(PKC) may have dual activities in the regulation of
glucose and fatty acid metabolism. When it is
over-activated by DAG (Diaglyceride), PKC may induce
insulin resistance by increasing serine
phosphorylation of insulin receptor as well as
insulin receptor substrate 1 (IRS-1). This happens
when DAG level is increased in cells under
obesity or lipid infusion. Oxidative stress
from hyperglycemia also induces PKC
over-activation.
On the other side, inactivation of PKC in mice may lead to reduction in energy expenditure promoting obesity and insulin resistance on high fat diet. The molecular basis of this activity remains unknown for PKC. A study in the current issue of Science may provide a possible mechanism. In the investigation of aging-related protein p66Shr, PKC was shown to activate this protein through phosphorylation, leading to production of free radicals in the mitochondria. This activity of PKC was demonstrated in an extreme condition where the cells were treated with H2O2 for apoptosis. Although regulation of the mitochondrial function by PKC was used to explain apoptosis in the study, the linkage of PKC to p66Shr suggests that in the physiological condition, PKC may use this channel to stimulate metabolism of glucose and fatty acids in the mitochondria. Mitochondrial production of free radicals is associated with metabolism of glucose or fatty acids. In obesity, PKC may use this linkage to induce mitochondrial dysfunction. These possibilities are not discussed in the paper, but it is worth to read it. Attached is PDF file of this paper.
In the current issue of Nature Medicine, there are several interesting papers related to molecular physiology related to metabolic syndrom. Below is the list.
Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins pp171 - 180
Tony K T Lam et al.
10.1038/nm1540
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcW0Eu
Article: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcX0Ev
Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity pp189 - 197
Jane A Leopold et al.
10.1038/nm1545
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLca0E5
Article: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcb0E6
Angiotensin II type 1 receptor blockade attenuates TGF-[beta]-induced failure of muscle regeneration in multiple myopathic states pp204 - 210
Ronald D Cohn et al.
10.1038/nm1536
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLce0EA
Article: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcf0EB
by Jianping at PBRC
—---------------------------------------------
Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225) 763-3163
Fax: (225) 763-2525
E-mail: yej@pbrc.edu
On the other side, inactivation of PKC in mice may lead to reduction in energy expenditure promoting obesity and insulin resistance on high fat diet. The molecular basis of this activity remains unknown for PKC. A study in the current issue of Science may provide a possible mechanism. In the investigation of aging-related protein p66Shr, PKC was shown to activate this protein through phosphorylation, leading to production of free radicals in the mitochondria. This activity of PKC was demonstrated in an extreme condition where the cells were treated with H2O2 for apoptosis. Although regulation of the mitochondrial function by PKC was used to explain apoptosis in the study, the linkage of PKC to p66Shr suggests that in the physiological condition, PKC may use this channel to stimulate metabolism of glucose and fatty acids in the mitochondria. Mitochondrial production of free radicals is associated with metabolism of glucose or fatty acids. In obesity, PKC may use this linkage to induce mitochondrial dysfunction. These possibilities are not discussed in the paper, but it is worth to read it. Attached is PDF file of this paper.
In the current issue of Nature Medicine, there are several interesting papers related to molecular physiology related to metabolic syndrom. Below is the list.
Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins pp171 - 180
Tony K T Lam et al.
10.1038/nm1540
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcW0Eu
Article: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcX0Ev
Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity pp189 - 197
Jane A Leopold et al.
10.1038/nm1545
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLca0E5
Article: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcb0E6
Angiotensin II type 1 receptor blockade attenuates TGF-[beta]-induced failure of muscle regeneration in multiple myopathic states pp204 - 210
Ronald D Cohn et al.
10.1038/nm1536
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLce0EA
Article: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcf0EB
by Jianping at PBRC
—---------------------------------------------
Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225) 763-3163
Fax: (225) 763-2525
E-mail: yej@pbrc.edu
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