Participation of the IKK-α/β complex in the inhibition of the TNF-α/NF-kB pathway by glycine: Possible involvement of a membrane receptor specific to adipocytes

被引：21

作者：

Contreras-Nunez, Erika ^{[1
]}

Blancas-Flores, Gerardo ^{[1
]}

Cruz, Miguel ^{[2
]}

Cesar Almanza-Perez, Julio ^{[1
]}

Gomez-Zamudio, Jaime H. ^{[2
]}

Luis Ventura-Gallegosc, Jose ^{[3
,4
]}

Zentella-Dehesa, Alejandro ^{[3
,4
]}

Roberto-Lazzarini ^{[5
]}

Roman-Ramos, Ruben ^{[1
]}

Javier Alarcon-Aguilar, Francisco ^{[1
]}

机构：

[1] Univ Autonoma Metropolitana Iztapalapa, DCBS, Dept Ciencias Salud, Lab Farmacol, Ave San Rafael Atlixco 186,AP 55-535, Mexico City 09340, DF, Mexico

[2] IMSS, Ctr Med Nacl Siglo 21, Hosp Especialidades, Unidad Invest Med Bioquim UIM, Av Cuauhtemoc 330, Mexico City, DF, Mexico

[3] UNAM, SZ, IIB, Dept Med Genom & Toxicol Ambiental, Cdmx, Mexico

[4] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Unidad Bioquim, Mexico City, DF, Mexico

[5] Univ Autonoma Metropolitana Iztapalapa, DCBS, Lab Div Microscopia Confocal, Ave San Rafael Atlixco 186,AP 55-535, Mexico City 09340, DF, Mexico

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2018年 / 102卷

关键词：

Glycine; Glycine receptors; Adipocytes; Inflammatory cytokines; IKK-alpha/beta complex; TNF-alpha/NF-kB; NF-KAPPA-B; TYROSINE PHOSPHORYLATION; 3T3-L1; ADIPOCYTES; CHLORIDE CHANNEL; KINASE COMPLEX; SERINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; INSULIN-RESISTANCE; GENE-EXPRESSION; ACTIVATION;

D O I：

10.1016/j.biopha.2018.03.048

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Glycine modulates inflammatory processes mediated by macrophages and adipocytes through decreasing the secretion of TNF-alpha, IL-6, and leptin, while increasing adiponectin. These effects have been associated with the inactivation of NF-kB in response to TNF-alpha, across an increase of its inhibitor IkB-alpha in adipocytes. However, glycine upstream mainly influences the IkB kinase (IKK) complex, a multi-protein kinase complex considered a critical point in regulation of the NF-kB pathway; whether that is responsible for the TNF-alpha-induced phosphorylation of IkB has not been explored. Additionally, although previous studies have described glycine interactions with specific receptors (GlyR) in different immune system cell types, it is currently unknown whether adipocytes present GlyR. In this research, participation of the IKK-alpha/beta complex in the inhibition of the TNF-alpha/NF-kB pathway by glycine was evaluated and associated with the synthesis and secretion of inflammatory cytokines in 3T3-L1 adipocytes. Furthermore, we also explored GlyR expression, its localization on the plasmatic membrane, intracellular calcium concentrations [Ca2+](i) and strychnine antagonist action over the GlyR in these cells. Glycine decreased the IKK-alpha/beta complex and the phosphorylation of NF-kB, diminishing the expression and secretion of IL-6 and TNF-alpha, but increasing that of adiponectin. GlyR expression and its fluorescence in the plasma membrane were increased in the presence of glycine. In addition, glycine decreased [ Ca2+] i; whereas strychnine + glycine treatment inhibited the activation of NF-kB observed with glycine. In conclusion, the reduction of TNF-alpha and IL-6 and suppression of the TNF-alpha/NF-kB pathway by glycine may be explained in part by inhibition of theIKK-alpha/beta complex, with a possible participation of GlyR in 3T3-L1 adipocytes.

引用

页码：120 / 131

页数：12