Department of Histology and Embryology, Yanbian University School of Medicine, 977 Gongyuan, Road, Jilin, Yanji, 133002, China.
Mol Biol Rep. 2020 Jan;47(1):141-149. doi: 10.1007/s11033-019-05115-9. Epub 2019 Oct 3.
In the precedent research conducted by the same team, it concluded that the activities in C-type natriuretic peptide (CNP)/cyclic guanosine monophosphate (cGMP)/cyclic adenosine monophosphate (cAMP)/β-type phospholipase C (PLCβ) pathways of rat antral smooth muscle were changed due to diabetes, which was the key pathogenetic mechanism for diabetic gastric dysmotility. As the follow-on step, this study was designed to probe into the downstream signaling pathway of CNP/PLCβ. The results showed that level of α-type protein kinase C (PKCα),cell membrane to cytoplasm ratio of PKCα, cell membrane to cytoplasmic ratio of βI-type protein kinase C (PKCβI) and level of Phosphor-PKCα (P-PKCα) were significantly reduced in diabetes rat antral smooth muscle samples. The content of tetraphosphate inositol (IP4) in gastric antral smooth muscle of diabetic rats reduced, and the content of diacyl-glycerol (DG) was unchanged. CNP significantly decreased the content of IP4 and DG, this effect was more obvious in diabetic rats. Subsequent to the addition of protein kinase A (PKA) blocker N-[2- (p-Bromocin-namylamino)ethyl]-5 -isoquinolinesulfonamide dihydrochloride (H-89) before CNP treatment, the inhibitory effect of CNP was reduced; subsequent to the addition of protein kinase G (PKG) blocker KT5823 before CNP treatment, the inhibitory effect of CNP was also reduced. With the addition of the combination of H-89 and KT5823 before CNP treatment, the inhibition by CNP could be offset. These results were concluded that CNP inhibited the activity of PKC family in rat smooth muscle and reduced the levels of IP4 and DG through the PKG/PKA-PLCβ pathways, causing inhibited muscular contractions, which may be a key pathogenetic factor for diabetic gastroparesis.
在同一团队进行的前期研究中，研究人员得出结论，由于糖尿病，大鼠胃窦平滑肌 C 型利钠肽（CNP）/环鸟苷酸（cGMP）/环腺苷酸（cAMP）/β-型磷脂酶 C（PLCβ）通路中的活动发生了变化，这是糖尿病性胃动力障碍的关键发病机制。作为后续步骤，本研究旨在探讨 CNP/PLCβ的下游信号通路。结果表明，糖尿病大鼠胃窦平滑肌中α型蛋白激酶 C（PKCα）水平、PKCα细胞膜到细胞质比值、βI 型蛋白激酶 C（PKCβI）细胞膜到细胞质比值和磷酸化 PKCα（P-PKCα）水平明显降低。糖尿病大鼠胃窦平滑肌中四磷酸肌醇（IP4）的含量减少，二酰基甘油（DG）的含量不变。CNP 显著降低 IP4 和 DG 的含量，这种作用在糖尿病大鼠中更为明显。在 CNP 处理前加入蛋白激酶 A（PKA）抑制剂 N-[2-（对溴辛基氨甲酰基）-5-异喹啉磺酰胺二盐酸盐]（H-89）后，CNP 的抑制作用减弱；在 CNP 处理前加入蛋白激酶 G（PKG）抑制剂 KT5823 后，CNP 的抑制作用也减弱。在 CNP 处理前加入 H-89 和 KT5823 的混合物后，CNP 的抑制作用可以抵消。这些结果表明，CNP 通过 PKG/PKA-PLCβ 通路抑制大鼠平滑肌中 PKC 家族的活性，降低 IP4 和 DG 水平，导致肌肉收缩受到抑制，这可能是糖尿病胃轻瘫的一个关键发病因素。
