Mitochondrial carnitine palmitoyltransferase 2 is involved in Nε-(carboxymethyl)-lysine-mediated diabetic nephropathy

Publication date: Available online 12 December 2019Source: Pharmacological ResearchAuthor(s): Jangho Lee, Ju-Yong Hyon, Jin Young Min, Yang Hoon Huh, Hyo Jung Kim, Hayoung Lee, Sung Ho Yun, Chi-Won Choi, Su Jeong Ha, Joon Park, Young-Ho Chung, Hye Gwang Jeong, Sang Keun Ha, Sung Keun Jung, YoonSook Kim, Eun Hee HanAbstractDiabetic nephropathy (DN) is the most common cause of end-stage renal disease in the world. Advanced glycation end products (AGEs) are thought to be involved in the pathogenesis of DN via multifactorial mechanisms including the generation of oxidative stress and overproduction of various growth factors and cytokines. AGEs are heterogeneous cross-linked sugar-derived proteins, and Nε-(carboxymethyl)-lysine (CML)-conjugated BSA is a major component of AGEs. However, the proteins involved in DN induction by CML have never been reported. Herein, we investigated specific protein regulators of AGE-mediated DN via proteomic analysis of streptozotocin (STZ)-induced diabetic mice kidneys. We identified 937, 976, and 870 proteins in control, STZ, and STZ + CML-BSA samples, respectively. Bioinformatics analysis identified several CML-mediated proteins potentially involved in kidney damage, activation of fatty acid oxidation (FAO), and mitochondrial dysfunction. Furthermore, we identified the CML-specific differential protein carnitine palmitoyltransferase 2 (CPT2), related to FAO. To confirm the effect of CPT2 and the CML-mediated mechanism, human renal tubular HK...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research