Downregulation of MAPK/MAK/MRK overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus

Sopić D., Miron (avtor), Ninić, Ana (avtor), Ostanek, Barbara (avtor), Bojanin, Dragana (avtor), Milenković, Tatjana (avtor), Munjas, Jelena (avtor), Mihajlović, Marija (avtor), Vekić, Jelena (avtor), Marc, Janja (avtor), Kalimanovska Spasojevič, Vesna (avtor)

Background Type 1 diabetes mellitus (T1DM) is one of the most common endocrine diseases in children. T-cell autoreactivity toward b-cells is controlled by significant changes in metabolism of T cells. Mammalian target of rapamycin (mTOR) is an important intracellular regulator of metabolism and cell growth. MAPK/MAK/MRK overlapping kinase 1 (MOK1) is one of the less known regulators of mTOR. We sought to investigate if MOK1 and mTOR mRNA levels in peripheral blood mononuclear cells (PBMCs) of T1DM pediatric patients are different compared to healthy subjects. Methods This study included 172 adolescents with T1DM and 36 healthy adolescent volunteers designated for control group (CG). MOK1 and mTOR mRNA levels were determined in PBMCs by qPCR. Results T1DM patients have significant downregulation of MOK1 mRNA levels in PBMCs compared CG (P=0.018), while there was no significant difference in mTOR mRNA levels (P=0.891). Furthermore, in T1DM patients, MOK1 significantly correlated with age, triglycerides and mTOR, while mTOR correlated significantly with BMI and systolic blood pressure. Overweight T1DM subjects had significantly lower MOK1 (P=0.034) and mTOR (P=0.017) mRNA levels, together with significantly higher levels of systolic blood pressure (P<0.001), total cholesterol (P=0.001), LDL-cholesterol (P=0.001) and CRP (P<0.001). Multi - variate analysis showed that MOK1 was independently negatively associated with T1DM when adjusted for sex, age, HDL-C and CRP (OR=0.417 (95%CI: 0.175-0.997), p=0.049). Conclusions Our study demonstrated for the first time that T1DM is associated with MOK1 downregulation. In addition, downregulation of both mTOR and MOK1 gene expressions was associated with cardiovascular risk factors in overweight T1DM patients.

• Jezik: Angleški jezik
• Ključne besede: type 1 Diabetes mellitus, Mammalian target of rapamycin, MAPK/MAK/MRK overlapping kinase 1
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: Str. 282–289
• Številčenje: Vol. 41, no. 3
• PID: 20.500.12556/RUL-144332
• UDK: 616.379-008.64
• ISSN pri članku: 1452-8266
• DOI: 10.5937/jomb0-33220
• COBISS.SI-ID: 141569283
• Datum objave v RUL: 15.02.2023

Gradivo je del revije

• Naslov: Journal of Medical Biochemistry
• Skrajšan naslov: J. Med. Biochem.
• Založnik: Society of Medical Biochemists of Serbia
• ISSN: 1452-8266
• COBISS.SI-ID: 519356441

Sekundarni jezik

• Jezik: Slovenski jezik
• Naslov: Nishodna regulacija MAPK/MAK/MRK preklapajuče kinaze u mononuklearnim ćelijama periferne krvi pedijatrijskih pacijenata sa tip1 Diiabetes mellitus-om

Izvleček

Uvod: Dijabetes melitus tip 1 (T1DM) jedno je od največih endokrinih oboljenja kod dece. Autoreaktivnost T-čelija prema beta-čelijama kontroliče se značajnim promenama u metabolizmu T }elija. Cilj delovanja rapamicina kod sisara je važan unutarćelijski regulator metabolizma i rasta ćelija. MAPK/MAK/MRK preklapaju}e kinaze koja se preklapa (MOK1) jedan je od manje poznatih regulatora mTOR-a. Cilj istraživanja je bio da se ispita da li su nivoi iRNK MOK1 i mTOR u mononuklearnim }elijama periferne krvi različiti kod pedijatrijskih pacijenata sa T1DM u odnosu na zdrave ispitanike. Metode: Ovo istraživanje je obuhvatilo 172 adolescenta sa T1DM i 36 zdravih adolescenata dobrovoljaca koji su činili kontrolnu grupu (CG). Nivoi MOK1 i mTOR mRNA određeni su u PBMC-ima pomoću qPCR-a. Rezultati: Pacijenti sa T1DM imali su značajno niže nivoe iRNK MOK1 u PBMC u odnosu na CG, dok razlike u nivoima iRNK mTOR nisu bile zna~ajne (P = 0,891). Štaviše, kod pacijenata sa T1DM, MOK1 je značajno korelirao sa godinama, trigliceri dima i mTOR, dok je mTOR značajno korelirao sa BMI i sistolnim krvnim pritiskom. Ispitanici sa prekomernom težinom T1DM imali su znaćajno niže nivoe iRNK MOK1 (P = 0,034) i mTOR (P = 0,017), zajedno sa značajno večim nivoima sistolnog krvnog pritiska (P <0,001), ukupnog holesterola (P = 0,001), LDL-holesterola (P = 0,001) i CRP (P <0,001). Multivarijantna analiza je pokazala da je MOK1 nezavisno negativno povezan sa HDL-C and CRP (OR=0.417 (95%CI: 0.175–0.997), p=0.049). Zaključak: Naša studija je prva koja je pokazala da je T1DM udružen sa nishodnom regulacijom MOK1. Pored toga, snižena regulacija ekspresije gena mTOR i MOK1 bila je povezana sa kardiovaskularnim faktorima rizika kod pacije nata sa T1DM sa prekomernom težinom.

• Ključne besede: Diabetes mellitus tip 1, tarča rapamicina pri sesalcih, prekrivajoča se MAPK/MAK/MRK kinaza, sladkorna bolezen tip 1

Projekti

• Financer: MESTD - Ministry of Education, Science and Technological Development of Republic of Serbia
• Program financ.: Ministry of Education, Science and Technological Development of Republic of Serbia
• Številka projekta: 175035
• Naslov: Interactive role of dyslipidemia, oxidative stress and inflammation in atherosclerosis and other diseases: genetic and biochemical markers

• Financer: Drugi - Drug financer ali več financerjev
• Program financ.: CEEPUS
• Številka projekta: CIII-SI0611-08-1819