• Je něco špatně v tomto záznamu ?

Transketolase Activity but not Thiamine Membrane Transport Change in Response to Hyperglycaemia and Kidney Dysfunction

K. Chalásová, L. Pácal, A. Pleskačová, L. Knopfová, J. Řehořová, M. Tomandlová, J. Tomandl, K. Kaňková,

. 2018 ; 126 (4) : 255-262. [pub] 20170926

Jazyk angličtina Země Německo

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc18033699

Grantová podpora
NV16-28040A MZ0 CEP - Centrální evidence projektů

AIM: Pentose phosphate pathway (PPP) with key enzyme transketolase (TKT), represents a potentially 'protective' mechanism in hyperglycaemia. Diabetic kidney disease (DKD), a common complication of both type 1 and type 2 diabetes associated with significant morbidity and mortality, represents the most common cause of chronic kidney disease (CKD). We hypothesized that protective PPP action in diabetes and eventually even more severely in concomitant DKD might be compromised by limited intracellular availability of an active TKT cofactor thiamine diphosphate (TDP). METHODS: Effect of hyperglycaemia on gene expression and protein levels of key PPP loci was studied in vitro using human cell lines relevant to diabetes (HUVEC and HRGEC) and (together with measurement of TKT activity, plasma thiamine and erythrocyte TDP concentration) in vivo in diabetic vs. non-diabetic subjects with comparable renal function (n=83 in total). RESULTS: Hyperglycaemia significantly decreased protein levels of RFC-1, THTR1, THTR2 and TKT (P<0.05) in vitro. Analysis of blood samples from CKD patients with and without diabetes and from controls did not reveal any difference in gene expression and protein levels of thiamine transporters while TKT activity and TDP in erythrocytes gradually increased with decreasing kidney function being highest in patients with CKD3-4 of both diabetic and non-diabetic aetiology. Hyperglycaemia and uremic serum mimicking CKD in diabetes did not affect TKT activity in vitro (P<0.05). CONCLUSION: Both in vitro and human experiments showed decrease or unchanged expression, respectively, of thiamine transporters induced by hyperglycaemia while TKT activity in parallel with intracellular TDP was increased in CKD patients with or without diabetes. Therefore, lack of adaptive increase of thiamine transmembrane transport allowing further increase of TKT activity might contribute to compromised PPP function in diabetes and CKD and to the development of glycotoxic injury.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc18033699
003      
CZ-PrNML
005      
20191002081711.0
007      
ta
008      
181008s2018 gw f 000 0|eng||
009      
AR
024    7_
$a 10.1055/s-0043-115009 $2 doi
035    __
$a (PubMed)28950391
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a gw
100    1_
$a Chalásová, Katarína, $d 1986- $7 mub2017949800 $u Department of Pathophysiology, Masaryk University, Brno.
245    10
$a Transketolase Activity but not Thiamine Membrane Transport Change in Response to Hyperglycaemia and Kidney Dysfunction / $c K. Chalásová, L. Pácal, A. Pleskačová, L. Knopfová, J. Řehořová, M. Tomandlová, J. Tomandl, K. Kaňková,
520    9_
$a AIM: Pentose phosphate pathway (PPP) with key enzyme transketolase (TKT), represents a potentially 'protective' mechanism in hyperglycaemia. Diabetic kidney disease (DKD), a common complication of both type 1 and type 2 diabetes associated with significant morbidity and mortality, represents the most common cause of chronic kidney disease (CKD). We hypothesized that protective PPP action in diabetes and eventually even more severely in concomitant DKD might be compromised by limited intracellular availability of an active TKT cofactor thiamine diphosphate (TDP). METHODS: Effect of hyperglycaemia on gene expression and protein levels of key PPP loci was studied in vitro using human cell lines relevant to diabetes (HUVEC and HRGEC) and (together with measurement of TKT activity, plasma thiamine and erythrocyte TDP concentration) in vivo in diabetic vs. non-diabetic subjects with comparable renal function (n=83 in total). RESULTS: Hyperglycaemia significantly decreased protein levels of RFC-1, THTR1, THTR2 and TKT (P<0.05) in vitro. Analysis of blood samples from CKD patients with and without diabetes and from controls did not reveal any difference in gene expression and protein levels of thiamine transporters while TKT activity and TDP in erythrocytes gradually increased with decreasing kidney function being highest in patients with CKD3-4 of both diabetic and non-diabetic aetiology. Hyperglycaemia and uremic serum mimicking CKD in diabetes did not affect TKT activity in vitro (P<0.05). CONCLUSION: Both in vitro and human experiments showed decrease or unchanged expression, respectively, of thiamine transporters induced by hyperglycaemia while TKT activity in parallel with intracellular TDP was increased in CKD patients with or without diabetes. Therefore, lack of adaptive increase of thiamine transmembrane transport allowing further increase of TKT activity might contribute to compromised PPP function in diabetes and CKD and to the development of glycotoxic injury.
650    _2
$a dospělí $7 D000328
650    _2
$a senioři $7 D000368
650    _2
$a biologický transport $7 D001692
650    _2
$a diabetes mellitus 2. typu $x metabolismus $7 D003924
650    _2
$a diabetické nefropatie $x metabolismus $7 D003928
650    _2
$a erytrocyty $x metabolismus $7 D004912
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a lidé $7 D006801
650    _2
$a hyperglykemie $x metabolismus $7 D006943
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    _2
$a chronická renální insuficience $x metabolismus $7 D051436
650    _2
$a thiamin $x metabolismus $7 D013831
650    _2
$a transketolasa $x metabolismus $7 D014174
655    _2
$a časopisecké články $7 D016428
700    1_
$a Pácal, Lukáš $u Department of Pathophysiology, Masaryk University, Brno.
700    1_
$a Pleskačová, Anna $u Department of Pathophysiology, Masaryk University, Brno. Department of Biochemistry, Masaryk University, Brno.
700    1_
$a Knopfová, Lucia $u Department of Experimental Biology, Faculty of Science, Masaryk University, Brno. International Clinical Research Center, Center for Biological and Cellular Engineering, St. Anne's University Hospital.
700    1_
$a Řehořová, Jitka $u Department of Gastroenterology, University Hospital Brno, Brno, Czech Republic.
700    1_
$a Tomandlová, Marie $7 xx0230817 $u Department of Biochemistry, Masaryk University, Brno.
700    1_
$a Tomandl, Josef $u Department of Pathophysiology, Masaryk University, Brno. Department of Biochemistry, Masaryk University, Brno.
700    1_
$a Kaňková, Kateřina $u Department of Pathophysiology, Masaryk University, Brno.
773    0_
$w MED00009707 $t Experimental and clinical endocrinology & diabetes official journal, German Society of Endocrinology [and] German Diabetes Association $x 1439-3646 $g Roč. 126, č. 4 (2018), s. 255-262
856    41
$u https://pubmed.ncbi.nlm.nih.gov/28950391 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20181008 $b ABA008
991    __
$a 20191002082119 $b ABA008
999    __
$a ok $b bmc $g 1340257 $s 1030693
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2018 $b 126 $c 4 $d 255-262 $e 20170926 $i 1439-3646 $m Experimental and clinical endocrinology & diabetes $n Exp Clin Endocrinol Diabetes $x MED00009707
GRA    __
$a NV16-28040A $p MZ0
LZP    __
$a Pubmed-20181008

Najít záznam

Citační ukazatele

Možnosti archivace