The level of ADM, SLC1A3, HSPA5 and PDGFC gene expressions in obese adolescents and adult men

Y. Viletska, D. Minchenko, V. Davydov, O. Minchenko
Taras Shevchenko National University of Kyiv, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv; SI "Institute of Children and Adolescent Health Care, NAMS Ukraine", Kharkiv; Palladin Institute of Biochemistry, Kyiv

Abstract


The aim of this work was to analyze the relative level of the expression of ADM (adrenomedullin), SLC1A3 (glial high affinity glutamate
transporter), HSPA5 (heat shock protein family A member 5) and PDGFC (platelet derived growth factor C) genes, which encoding poly-functional
proteins, in adolescents blood and adipose tissue in adult men with obesity without insulin resistance to determine their possible role in the
development of obesity and its complications. It was shown that relative expression level of SLC1A3, HSPA5 and PDGFC genes in the blood of
obese adolescents without insulin resistance was significantly increased as compared to control group of relative healthy individuals of the same
age without signs of obesity. At the same time, the expression level of ADM gene did not change significantly in these obese adolescents. It was
also shown that in subcutaneous adipose tissue of obese adult men without insulin resistance the relative level of SLC1A3 and PDGFC gene
expressions was decreased, but ADM and HSPA5 genes – increased as compared to control group. The increased level of ADM gene expression,
which has hypotensive activity, controls corticotrophin, leptin, endothelin-1 and adiponectin secretion and is related to the development of insulin
resistance and metabolic syndrome as well as overexpressed in malignant tumors, possibly related to the development of obesity complications
including tumorigenesis. To a large extent, this also applies to increased expression of HSPA5 gene, which is involved in controlling various
metabolic pathways, both in and outside cells, found in the endoplasmic reticulum, nucleus, mitochondria, and cytosol, plays an important role in
the endoplasmic reticulum stress, obesity, insulin resistance and carcinogenesis. Therefore, the expression level of genes, which related to the
development of obesity and endoplasmic reticulum stress as well as proliferation processes, was significantly changed in the blood and adipose
tissue at obesity in gene-specific manner.


Keywords


gene expressions, ADM, SLC1A3, HSPA5, PDGFC, blood, adipose tissue, obesity

Full Text:

PDF>PDF

References


Minchenko D, Ratushna O, Bashta Y, Herasymenko R, Minchenko O. The expression of TIMP1, TIMP2, VCAN, SPARC, CLEC3B and E2F1 in subcutaneous adipose tissue of obese males and glucose intolerance. CellBio. 2013; Vol. 2(2):25–33.

Minchenko DO. Molecular bases of the development of obesity and its metabolic complications in children. Modern Pediatrics 2013;2(66):25–33.

Yamaoka M, Maeda N, Nakamura S, Kashine S, Nakagawa Y, Hiuge-Shimizu A, et al. A pilot investigation of visceral fat adiposity and gene expression profile in peripheral blood cells. // PLoS One 2012;7(10):e47377.

Ando H, Kumazaki M, Motosugi Y, Ushijima K, Maekawa T, Ishikawa E, et al. Impairment of peripheral circadian clocks precedes metabolic abnormalities in ob/ob mice. Endocrinology 2011;152(4):1347–54.

Yamaoka M, Maeda N, Takayama Y, Sekimoto R, Tsushima Y, Matsuda K, et al. Adipose hypothermia in obesity and its association with period homolog 1, insulin sensitivity, and inflammation in fat. PLoS One 2014;9(11):e112813.

Bravo R, Parra V, Gatica D, Rodriguez AE, Torrealba N, Paredes F, et al. Endoplasmic reticulum and the unfolded protein response: dynamics and metabolic integration. Int Rev Cell Mol Biol 2013;301:215-90.

Han J, Kaufman RJ. Measurement of the unfolded protein response to investigate its role in adipogenesis and obesity. Methods Enzymol 2014;538:135-50.

Minchenko DO, Davydov VV, Budreiko OA, Moliavko OS, Kulieshova DK, Tiazhka OV, et al. Expression of CСN2, IQSEC, RSPO1, DNAJC15, RIPK2, IL13RA2, IRS1, and IRS2 genes in blood cells of obese boys with and without insulin resistance. Fiziol Zh. 2015;61(1):10-8.

Aggarwal G, Ramachandran V, Javeed N, Arumugam T, Dutta S, Klee GG, et al. Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in β cells and mice. Gastroenterology 2012;143(6):1510-1517.

Zhou C, Zheng Y, Li L, Zhai W, Li R, Liang Z, et al. Adrenomedullin promotes intrahepatic cholangiocellular carcinoma metastasis and invasion by inducing epithelial-mesenchymal transition. Oncol. Rep 2015;34(2):610-6.

Zhang SY, Lv Y, Zhang H, Gao S, Wang T, Feng J, at al. Adrenomedullin 2 Improves Early Obesity-Induced Adipose Insulin

Resistance by Inhibiting the Class II MHC in Adipocytes. Diabetes 2016;65(8):2342-55.

Liao SB, Wong PF; WSO, Cheung BM, Tang F. Effects of adrenomedullin on tumour necrosis factor alpha, interleukins, endothelin-1, leptin, and adiponectin in the epididymal fat and soleus muscle of the rat. Horm Metab Res. 2013 Jan;45(1):31-7.

Di Liddo R, Bridi D, Gottardi M, De Angeli S, Grandi C, Tasso A, et al. Adrenomedullin in the growth modulation and differentiation of acute myeloid leukemia cells. Int J Oncol 2016;48(4):1659-69.

Lee A, Anderson AR, Beasley SJ, Barnett NL, Poronnik P, Pow DV. A new splice variant of the glutamate-aspartate transporter: cloning and immunolocalization of GLAST1c in rat, pig and human brains. J Chem Neuroanat 2012;43(1):52-63.

Son D, Na YR, Hwang ES, Seok SH. Platelet-derived growth factor-C (PDGF-C) induces anti-apoptotic effects on macrophages through Akt and Bad phosphorylation. J Biol Chem 2014;289(9):6225-6235.

Amin-Wetzel N, Saunders RA, Kamphuis MJ, Rato C, Preissler S, Harding HP, et al. A J-Protein Co-chaperone Recruits BiP to Monomerize IRE1 and Repress the Unfolded Protein Response. Cell 2017;171(7):1625-37.

Wang C, Cai L, Liu J, Wang G, Li H, Wang X, et al. MicroRNA-30a-5p Inhibits the Growth of Renal Cell Carcinoma by Modulating GRP78 Expression. Cell Physiol Biochem 2017;43(6):2405-19.

Kang JM, Park S, Kim SJ, Kim H, Lee B, Kim J, et al. KIAA1324 Suppresses Gastric Cancer Progression by Inhibiting the Oncoprotein GRP78. Cancer Res 2015;75(15) :3087-97.

Tsuchihara K, Ogura T, Fujioka R, Fujii S, Kuga W, Saito M, et al. Susceptibility of Snark-deficient mice to azoxymethane-induced colorectal tumorigenesis and the formation of aberrant crypt foci. // Cancer Sci 2008;99(4):677-82.

Minchenko OH, Tsymbal DO, Minchenko DO, Kubaichuk OO. Hypoxic regulation of MYBL1, MEST, TCF3, TCF8, GTF2B, GTF2F2 and SNAI2 genes expression in U87 glioma cells upon IRE1 inhibition. Ukr Biochem J 2016;88(6):52-62.

Received in editorial: 26.09.2018

Received the revised version: 29.10.2018

Signed for press: 29.10.2018


Refbacks

  • There are currently no refbacks.


Лицензия Creative Commons
This journal is available according to the Creative Commons License «Attribution» («Атрибуція») 4.0 Global (CC-BY).