PMID- 27472463
OWN - NLM
STAT- MEDLINE
DCOM- 20180130
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 32
DP  - 2016 Aug 9
TI  - Activation of proinflammatory signaling by 4-hydroxynonenal-Src adducts in aged 
      kidneys.
PG  - 50864-50874
LID - 10.18632/oncotarget.10854 [doi]
AB  - 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-kappaB (NF-kappaB) 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-kappaB 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-kappaB, 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.
FAU - Jang, Eun Ji
AU  - Jang EJ
AD  - Department of Pharmacy, Molecular Inflammation Research Center for Aging 
      Intervention (MRCA), Pusan National University, Busan, Republic of Korea.
FAU - Kim, Dae Hyun
AU  - Kim DH
AD  - Department of Pharmacy, Molecular Inflammation Research Center for Aging 
      Intervention (MRCA), Pusan National University, Busan, Republic of Korea.
FAU - Lee, Bonggi
AU  - Lee B
AD  - Department of Pharmacy, Molecular Inflammation Research Center for Aging 
      Intervention (MRCA), Pusan National University, Busan, Republic of Korea.
FAU - Lee, Eun Kyeong
AU  - Lee EK
AD  - Department of Pharmacy, Molecular Inflammation Research Center for Aging 
      Intervention (MRCA), Pusan National University, Busan, Republic of Korea.
FAU - Chung, Ki Wung
AU  - Chung KW
AD  - Department of Pharmacy, Molecular Inflammation Research Center for Aging 
      Intervention (MRCA), Pusan National University, Busan, Republic of Korea.
FAU - Moon, Kyoung Mi
AU  - Moon KM
AD  - Department of Pharmacy, Molecular Inflammation Research Center for Aging 
      Intervention (MRCA), Pusan National University, Busan, Republic of Korea.
FAU - Kim, Min Jo
AU  - Kim MJ
AD  - Department of Pharmacy, Molecular Inflammation Research Center for Aging 
      Intervention (MRCA), Pusan National University, Busan, Republic of Korea.
FAU - An, Hye Jin
AU  - An HJ
AD  - Department of Pharmacy, Molecular Inflammation Research Center for Aging 
      Intervention (MRCA), Pusan National University, Busan, Republic of Korea.
FAU - Jeong, Ji Won
AU  - Jeong JW
AD  - Department of Pharmacy, Molecular Inflammation Research Center for Aging 
      Intervention (MRCA), Pusan National University, Busan, Republic of Korea.
FAU - Kim, Ye Ra
AU  - Kim YR
AD  - Department of Pharmacy, Molecular Inflammation Research Center for Aging 
      Intervention (MRCA), Pusan National University, Busan, Republic of Korea.
FAU - Yu, Byung Pal
AU  - Yu BP
AD  - Department of Physiology, The University of Texas Health Science Center at San 
      Antonio, San Antonio, Texas, United States of America.
FAU - Chung, Hae Young
AU  - Chung HY
AD  - Department of Pharmacy, Molecular Inflammation Research Center for Aging 
      Intervention (MRCA), Pusan National University, Busan, Republic of Korea.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Aldehydes)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - K1CVM13F96 (4-hydroxy-2-nonenal)
SB  - IM
MH  - Aging/*metabolism/pathology
MH  - Aldehydes/*metabolism
MH  - Animals
MH  - Cellular Senescence/physiology
MH  - Humans
MH  - Inflammation/*metabolism
MH  - Kidney/metabolism/*pathology
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/physiology
MH  - src-Family Kinases/*metabolism
PMC - PMC5239442
OTO - NOTNLM
OT  - 4-HNE
OT  - Gerotarget
OT  - Src
OT  - aged kidney
OT  - cell senescence
OT  - inflammation
COIS- The authors declare no conflict of interest.
EDAT- 2016/07/30 06:00
MHDA- 2018/01/31 06:00
PMCR- 2016/08/09
CRDT- 2016/07/30 06:00
PHST- 2015/11/06 00:00 [received]
PHST- 2016/07/17 00:00 [accepted]
PHST- 2016/07/30 06:00 [pubmed]
PHST- 2018/01/31 06:00 [medline]
PHST- 2016/07/30 06:00 [entrez]
PHST- 2016/08/09 00:00 [pmc-release]
AID - 10854 [pii]
AID - 10.18632/oncotarget.10854 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Aug 9;7(32):50864-50874. doi: 10.18632/oncotarget.10854.