Department of Biochemistry and Molecular Biology, University of Debrecen, H-4032 Debrecen, Hungary.
Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, H-4032 Debrecen, Hungary.
Int J Mol Sci. 2020 May 29;21(11):3865. doi: 10.3390/ijms21113865.
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.
多功能组织转谷氨酰胺酶已被证明在几种细胞类型中作为具有 GTPase 活性的α1-肾上腺素能受体偶联 G 蛋白起作用。为了进一步探讨这种功能的病理生理意义，我们研究了α1-肾上腺素能受体激动剂苯肾上腺素在野生型和 TG2 小鼠体内的作用。与β3-肾上腺素能激动剂（CL-316,243）相比，苯肾上腺素的注射导致 TG2 小鼠的呼吸交换率长期下降和乳酸浓度降低，表明它们更喜欢利用脂肪酸而不是葡萄糖作为燃料。测量尾血压显示，苯肾上腺素在 TG2 小鼠中的血管收缩作用较弱，导致血液中的乳酸脱氢酶（LDH）同工酶水平较低。LDH 同工酶图谱表明野生型小鼠的肺、肝、肾、骨骼和心脏肌肉损伤更严重；后者通过更高水平的心特异性 CK-MB 得到证实。我们的数据表明，作为α1-肾上腺素能受体偶联 G 蛋白的 TG2 在α1-肾上腺素能受体介导的代谢过程和血管功能中具有重要的调节作用。
