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Ramachandran, S and Venugopal , A and Sathisha , K and Reshmi, G and Charles, S and Divya , G and Chandran, N S and Mullassari , A and Pillai, M R and Kartha, C C (2012) Proteomic profiling of high glucose primed monocytes identifies cyclophilin A as a potential secretory marker of inflammation in type 2 diabetes. Proteomics., 12(18). 2808-2821 . ISSN 1615-9861

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Abstract

Hyperglycemia is widely recognized to be a potent stimulator of monocyte activity, which is a crucial event in the pathogenesis of atherosclerosis. We analyzed the monocyte proteome for potential markers that would enhance the ability to screen for early inflammatory status in Type 2 diabetes mellitus (T2DM), using proteomic technologies. Monocytic cells (THP-1) were primed with high glucose (HG), their protein profiles were analyzed using 2DE and the downregulated differentially expressed spots were identified using MALDI TOF/MS. We selected five proteins that were secretory in function with the help of bioinformatic programs. A predominantly downregulated protein identified as cyclophilin A (sequence coverage 98%) was further validated by immunoblotting experiments. The cellular mRNA levels of cyclophilin A in various HG-primed cells were studied using qRT-PCR assays and it was observed to decrease in a dose-dependent manner. LC-ESI-MS was used to identify this protein in the conditioned media of HG-primed cells and confirmed by Western blotting as well as ELISA. Cyclophilin A was also detected in the plasma of patients with diabetes. We conclude that cyclophilin A is secreted by monocytes in response to HG. Given the paracrine and autocrine actions of cyclophilin A, the secreted immunophilin could be significant for progression of atherosclerosis in type 2 diabetes. Our study also provides evidence that analysis of monocyte secretome is a viable strategy for identifying candidate plasma markers in diabetes.

Item Type: Article
Uncontrolled Keywords: Cell biology / Hyperglycemia / Monocytes / Type 2 diabetes mellitus
Subjects: Cancer Research
Depositing User: Rgcb Library
Date Deposited: 22 Dec 2016 04:06
Last Modified: 04 Jul 2019 08:07
URI: http://rgcb.sciencecentral.in/id/eprint/46

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