Co-occurrence of Protein Crotonylation and 2-Hydroxyisobutyrylation in the Proteome of End-Stage Renal Disease

Dong, Jingjing1,2; Li, Yixi1,2; Zheng, Fengping2; Chen, Wenbiao2; Huang, Shaoying2; Zhou, Xianqing3; Wang, Kang2; Cai, Wanxia2; Liu, HaiPing4; Yin, Lianghong1; Li, Qiang5; Tang, Donge2; Dai, Yong2,3

2021-06-22

10.1021/acsomega.1c01161

ACS Omega   影响因子和分区

2470-1343

End-stage renal disease (ESRD) is gradually becoming a major public healthcare burden worldwide. Post-translational modifications carrying epigenetic information play a crucial role in the pathogenesis of many chronic diseases. We performed lysine crotonylation (KCr) and lysine 2-hydroxyisobutyrylation (Khib) analyses with liquid chromatography-tandem mass spectrometry to obtain a comprehensive profile and reveal the specific pathogenesis of peripheral blood mononuclear cells in ESRD patients. 218 overlap proteins among differentially modified proteins (DMPs) of both 2-hydroxyisobutyrylation and crotonylation were identified. KEGG analysis enriched pathways of protein processing in endoplasmic reticulum (ER) and glycolysis/ gluconeogenesis which is closely related with cell apoptosis. In Bip, a master regulator in the ER, eight sites were identified as having both KCr and Khib modifications. Five differentially KCr modification sites and three differentially Ithib-modified sites were detected between ESRD patients and normal controls. Besides Bip, other proteins (GRP94, CNX, CRT, PDIs, GIcII, ERP57, Bap31, Hsp70, and Hsp90) happened both KCr and Ithib modifications. Nine DMPs having both KCr and Khib modifications were related to the glycolysis/gluconeogenesis pathway containing two key regulatory enzymes of hexokinase-1 and pyruvate kinase. The two most abundant dual modification proteins were ENO1 and PGK1 with 15 sites and 8 sites, respectively. Lysine residue 1<228 with both KCr and Khib modifications in ENO1 was on its surface and made it accessible for p300 mediating dynamic modifications. Overall, we hypothesize that KCr and Khib comodifications may influence the number of immunocytes and further induce immune senescence in ESRD patients through the glycolysis/gluconeogenesis pathway and protein processing in the ER process, which may be a potential therapeutic direction in the future.

SCI

英语

通讯

Key Renal Laboratory of Shenzhen[ZDSYS2015430161623417] ; Guangxi Key Laboratory of Metabolic Diseases Research[20-065-76] ; Science and Technology Plan of Shenzhen["JCYJ20190807153405508","JCYJ201803 06140810282"] ; Guangdong Provincial High-level Clinical Key Specialties[SZGSP001] ; Natural Science Foundation of Guangxi[2017GXNSFAA198185] ; Key Research and Development Program of Guangdong Province[2019B020229001] ; 2019 Dongguan Social Science and Technology Development (key) project[201950715002195]

Chemistry

Chemistry, Multidisciplinary

WOS:000665649000027

AMER CHEMICAL SOC

Web of Science

1.Jinan Univ, Affiliated Hosp 1, Inst Nephrol & Blood Purificat, Guangzhou 510632, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ,Shen Hen Engn Res Ctr Autoimmune Dis, Shenzhen Peoples Hosp,Guangdong Prov Engn Res Ctr, Clin Med Res Ctr,Affiliated Hosp 1,Clin Med Coll, Shenzhen 518020, Guangdong, Peoples R China
3.Southern Med Univ, Affiliated Hosp 924, Guangxi Key Lab Metab Dis Res, Guilin 541002, Peoples R China
4.Second Peoples Hosp Lianping Cty, Heyuan 517139, Guangdong, Peoples R China
5.Guangzhou Univ Tradit Chinese Med, Dongguan Hosp, Dongguan 523000, Guangdong, Peoples R China

Dong, Jingjing,Li, Yixi,Zheng, Fengping,et al. Co-occurrence of Protein Crotonylation and 2-Hydroxyisobutyrylation in the Proteome of End-Stage Renal Disease[J]. ACS Omega,2021,6(24).

Dong, Jingjing.,Li, Yixi.,Zheng, Fengping.,Chen, Wenbiao.,Huang, Shaoying.,...&Dai, Yong.(2021).Co-occurrence of Protein Crotonylation and 2-Hydroxyisobutyrylation in the Proteome of End-Stage Renal Disease.ACS Omega,6(24).

Dong, Jingjing,et al."Co-occurrence of Protein Crotonylation and 2-Hydroxyisobutyrylation in the Proteome of End-Stage Renal Disease".ACS Omega 6.24(2021).