title: Identification of phosphorylated MYL12B as a potential plasma biomarker for septic acute kidney injury using a quantitative proteomic approach.
abstract: Acute kidney injury (AKI) is a common and increasingly encountered complication in hospitalized patients with critical illness in intensive care units (ICU). According to the etiology, Sepsis-induced AKI (SAKI) is a leading contributor to AKI and significantly has very poor prognosis, which might be related to the late detection when the elevation of BUN and serum creatinine (SCr) is used. Many genes are up-regulated in the damaged kidney with the corresponding protein products appearing in plasma and urine. Some of these are candidate biomarkers for more timely diagnosis of SAKI. Therefore, extensive research efforts over this past decade have been directed at the discovery and validation of novel SAKI biomarkers to detect injury prior to changes in kidney function, a number of serum and urinary proteins, including NGAL, KIM-1, cystatin-C, IL-18, and L-FABP, have been identified for predicting SAKI before a rise in BUN and serum creatinine in several experimental and clinical trainings. Unfortunately, an ideal biomarker of SAKI with highly sensitivity and specificity has not been identified yet. Recent progresses in quantitative proteomics have offered opportunities to discover biomarkers for SAKI. In the present study, kidney tissue samples from SAKI mice were analyzed by two-dimensional differential gel electrophoresis (2D-DIGE), and 4 up-regulated proteins, which were actin (ACTB), myosin regulatory light chain 12B (MYL12B), myosin regulatory light polypeptide 9 (MYL9), and myosin regulatory light chain 12A (MYL12A) were identified by matrix assisted laser desorption ionization-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF MS). Among all the varied proteins, MYL12B was validated by western blot. Interestingly, there was no change between the SAKI and control kidney tissues, however, phosphorylated MYL12B was detected to be consistent with the proteomics data. Furthermore, phosphorylated MYL12B was found similarly to be increased in SAKI plasma, while MYL12B was changeless in plasma of control group. Taking together, phosphorylated MYL12B may be employed as a potential plasma biomarker for the early diagnosis of SAKI.
authors.affiliation: Southern Medical UniversityGuangzhou 510515, Guangdong, China; Department of Nephrology, The Third Hospital of Zhengzhou 450000Zhengzhou, Henan, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Hematology, The Third Hospital of Zhengzhou 450000 Zhengzhou, Henan, China.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Dong
authors.affiliation: Southern Medical University Guangzhou 510515, Guangdong, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Li
authors.affiliation: Southern Medical University Guangzhou 510515, Guangdong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Intensive Care Unit, General Hospital of Guangzhou Military CommandGuangzhou 510010, Guangdong, China; Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLAGuangzhou 510010, Guangdong, China.
authors.forename: Qiu-Lin
authors.initials: QL
authors.lastname: Xu
authors.affiliation: Department of Intensive Care Unit, General Hospital of Guangzhou Military CommandGuangzhou 510010, Guangdong, China; Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLAGuangzhou 510010, Guangdong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Su
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D019295:Computational Biology; D004195:Disease Models, Animal; D042241:Early Diagnosis; D007668:Kidney / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D018994:Myosin Light Chains / Q000097:blood*; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D018805:Sepsis / Q000150:complications; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D057825:Two-Dimensional Difference Gel Electrophoresis; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C000611837:MYL12B protein, mouse; D018994:Myosin Light Chains
keywords: MYL12B; SAKI; biomarker; phosphorylation; plasma; proteomic
references.citation: Crit Care. 2008;12(2):R47
references.pmid: 18402655
references.citation: Semin Nephrol. 2015 Jan;35(1):85-95
references.pmid: 25795502
references.citation: J Am Soc Nephrol. 2003 Apr;14(4):1022-30
references.pmid: 12660337
references.citation: Pediatr Nephrol. 2014 Jan;29(1):1-12
references.pmid: 23400860
references.citation: Am J Med. 2005 Aug;118(8):827-32
references.pmid: 16084171
references.citation: Surgery. 1979 Feb;85(2):205-11
references.pmid: 419461
references.citation: Pediatr Nephrol. 2010 Aug;25(8):1453-61
references.pmid: 20512652
references.citation: J Clin Invest. 2009 Oct;119(10):2868-78
references.pmid: 19805915
references.citation: Crit Care Med. 2008 Apr;36(4 Suppl):S146-51
references.pmid: 18382186
references.citation: Nephrol Dial Transplant. 2008 Mar;23(3):904-9
references.pmid: 18065435
references.citation: Proteomics. 2003 Jan;3(1):36-44
references.pmid: 12548632
references.citation: Expert Opin Med Diagn. 2008 Apr;2(4):387-398
references.pmid: 19079800
references.citation: Nat Rev Mol Cell Biol. 2009 Nov;10(11):778-90
references.pmid: 19851336
references.citation: Kidney Int. 2007 Jul;72(2):208-12
references.pmid: 17507907
references.citation: Med Intensiva. 2011 Oct;35(7):424-32
references.pmid: 21549449
references.citation: Nat Clin Pract Nephrol. 2006 Jul;2(7):364-77
references.pmid: 16932465
references.citation: Clin J Am Soc Nephrol. 2007 May;2(3):431-9
references.pmid: 17699448
references.citation: Prim Care. 2014 Dec;41(4):779-802
references.pmid: 25439534
references.citation: Biochem J. 2011 Feb 15;434(1):171-80
references.pmid: 21126233
references.citation: Semin Nephrol. 2015 Jan;35(1):2-11
references.pmid: 25795495
references.citation: Heart Lung Vessel. 2015;7(1):64-73
references.pmid: 25861592