Activation of proinflammatory signaling by 4-hydroxynonenal-Src adducts in aged kidneys.

Activation of proinflammatory signaling by 4-hydroxynonenal-Src adducts in aged kidneys.

Oncotarget. 2016 Jul 26;

Authors: Jang EJ, Kim DH, Lee B, Lee EK, Chung KW, Moon KM, Kim MJ, An HJ, Jeong JW, Kim YR, Yu BP, Chung HY

Abstract
In our previous study, reactive 4-hydroxy-2-nonenal (4-HNE) was shown to activate Src (a non-receptor tyrosine kinase) by forming an adduct on binding with a specific residue of Src, leading to the activation of proinflammatory signaling pathways in cultured cells. However, to date, the deleterious roles of 4-HNE in inflammatory signaling activation in kidneys during aging have not been explored. The purpose of the present study was to document the mechanisms by which 4-HNE induces inflammation in the kidney during aging. Initial experiments revealed that activated nuclear factor-κB (NF-κB) expression was caused by 4-HNE activation, which suppressed transcriptional activity in the aged kidney. Treatment of human umbilical vein endothelial cells with 4-HNE revealed that Src caused senescence via NF-κB activation. Furthermore, our immunohistochemistry data showed that 4-HNE-adducted Src significantly increased in aged kidney tissues. The data showed age-related upregulation of downstream signaling molecules such as mitogen activated protein kinases (MAPKs), activator protein-1 (AP-1), NF-κB, and COX-2 in a cell culture cell system.Taken together, the results of this study show that the formation of adducts between 4-HNE and Src activates inflammatory signaling pathways in the aged kidney, contributing to age-related nephropathy.

PMID: 27472463 [PubMed - as supplied by publisher]

from Head and Neck on PubMed via xlomafota13 on Inoreader http://ift.tt/2ajKgXI


http://ift.tt/2ayg0oT