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Proinflammatory interleukin-1 cytokines increase mesangial cell hexokinase activity and hexokinase II isoform abundance.
- Source :
-
American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2004 Aug; Vol. 287 (2), pp. C548-57. Date of Electronic Publication: 2004 Apr 07. - Publication Year :
- 2004
-
Abstract
- Mesangial cell hexokinase (HK) activity is increased by a diverse array of factors that share both an association with pathological conditions and a common requirement for classic MAPK pathway activation. To better understand the relationship between glucose (Glc) metabolism and injury and to indirectly test the hypothesis that these changes constitute a general adaptive response to insult, we have sought to identify and characterize injury-associated factors that couple to mesangial cell HK regulation. Proinflammatory interleukin-1 (IL-1) cytokines activate the MAPK pathway and have known salutary effects in this cell type. We therefore examined their ability to influence mesangial cell HK activity, Glc utilization, MAPK pathway activation, and individual HK isoform abundance. IL-1beta increased HK activity in both a time- and concentration-dependent manner: activity increased maximally by approximately 50% between 12 and 24 h with an apparent EC(50) of 3 pM. IL-1alpha mimicked, but did not augment, the effects of IL-1beta. Specific IL-1 receptor antagonism and selective MAPK/ERK kinase or upstream Ras inhibition prevented these increases, whereas PKC inhibition did not. Changes in HK activity were associated with both increased Glc metabolism and selective increases in HKII isoform abundance. We conclude that IL-1 cytokines can regulate cellular Glc phosphorylating capacity via an IL-1 receptor-, Ras-, and classic MAPK pathway-mediated increase in HKII abundance. These findings suggest a novel, previously undescribed mechanism whereby metabolism may be coupled to inflammation and injury.
- Subjects :
- Animals
Dose-Response Relationship, Drug
Enzyme Inhibitors pharmacology
Glomerular Mesangium cytology
Glucose metabolism
MAP Kinase Signaling System drug effects
MAP Kinase Signaling System physiology
Mice
Protein Kinase C antagonists & inhibitors
Protein Kinase C metabolism
Receptors, Interleukin-1 antagonists & inhibitors
Receptors, Interleukin-1 metabolism
Glomerular Mesangium enzymology
Hexokinase metabolism
Interleukin-1 pharmacology
Isoenzymes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6143
- Volume :
- 287
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Cell physiology
- Publication Type :
- Academic Journal
- Accession number :
- 15070811
- Full Text :
- https://doi.org/10.1152/ajpcell.00126.2003