Transglutaminase 2 Has Metabolic and Vascular Regulatory Functions Revealed by In Vivo Activation of Alpha1-Adrenergic Receptor.
The multifunctional tissue transglutaminase has been demonstrated to act as α1-adrenergic receptor-coupled G protein with GTPase activity in several cell types. To explore further the pathophysiological significance of this function we investigated the in vivo effects of the α1-adrenergic receptor agonist phenylephrine comparing responses in wild type and TG2-/- mice. Injection of phenylephrine, but not a beta3-adrenergic agonist (CL-316,243), resulted in the long-term decline of the respiratory exchange ratio and lower lactate concentration in TG2-/- mice indicating they preferred to utilize fatty acids instead of glucose as fuels. Measurement of tail blood pressure revealed that the vasoconstrictive effect of phenylephrine was milder in TG2-/- mice leading to lower levels of lactate dehydrogenase (LDH) isoenzymes in blood. LDH isoenzyme patterns indicated more damage in lung, liver, kidney, skeletal, and cardiac muscle of wild type mice; the latter was confirmed by a higher level of heart-specific CK-MB. Our data suggest that TG2 as an α1-adrenergic receptor-coupled G protein has important regulatory functions in alpha1-adrenergic receptor-mediated metabolic processes and vascular functions.
['Lénárt|Kinga|K|', 'Pap|Attila|A|', 'Pórszász|Róbert|R|', 'V Oláh|Anna|A|', 'Fésüs|László|L|0000-0002-3338-2362', 'Mádi|András|A|']
D058646:Adrenergic alpha-1 Receptor Agonists D058668:Adrenergic alpha-1 Receptor Antagonists D000818:Animals D001808:Blood Vessels D004149:Dioxoles D005227:Fatty Acids D019204:GTP-Binding Proteins D005947:Glucose D007668:Kidney D007770:L-Lactate Dehydrogenase D008099:Liver D008168:Lung D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D009132:Muscles D010656:Phenylephrine D000091345:Protein Glutamine gamma Glutamyltransferase 2 D018340:Receptors, Adrenergic, alpha-1 D011503:Transglutaminases D014661:Vasoconstriction
respiratory exchange ratio blood pressure lactate dehydrogenase CLAMS creatine kinase MB heart failure transglutaminase 2 KO