Ontogeny of Na(+)/L-carnitine transporter and of gamma-trimethylaminobutyraldehyde dehydrogenase and gamma-butyrobetaine hydroxylase genes expression in rat kidney.
The kidney synthesizes L-carnitine and reabsorbs it via the Na(+)/L-carnitine cotransporter OCTN2. This study investigates the ontogeny of OCTN2, gamma-trimethylaminobutyraldehyde dehydrogenase (TMABA-DH) and gamma-butyrobetaine hydroxylase (BBH) in rat kidneys. Foetuses, newborn, suckling, weaning and adult rats were used. The apical membranes of foetal and newborn rat kidneys express OCTN2 transport activity, which is up-regulated by age. Maturation significantly increased the V(max) of this transport system without changing the apparent K(t), which excludes a maturation-related expression of different transporter isoforms. Northern analysis showed a 3.7kb transcript for OCTN2 in all the ages tested. Northern and RT-PCR assays revealed that maturation increased renal expression of OCTN2 mRNA. Foetuses express TMABA-DH mRNA and this expression increased during postnatal life. BBH mRNA, however, was detected during the suckling period onwards and its abundance was not changed significantly by maturation. This study reports for the first time that, in rat kidneys: (i) an apical OCTN2 transporter is active in rat foetuses, (ii) ontogeny up-regulates OCTN2 activity by increasing the density and/or turnover of the transporters, (iii) the maturation-related changes in OCTN2 are in part mediated by transcriptional mechanism(s) and (iv) the expression of both, TMABA-DH and BBH mRNA is ontogenically regulated. Some of these results were published as an abstract (García-Delgado et al., 2003).
García-Delgado
Marta
M
Departamento Fisiología y Zoología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
Peral
María J
MJ
Durán
Juan M
JM
García-Miranda
Pablo
P
Calonge
Maria L
ML
Ilundáin
Anunciación A
AA
D000375:Aging / Q000502:physiology; D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002331:Carnitine / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D000074058:Solute Carrier Family 22 Member 5; D050563:gamma-Butyrobetaine Dioxygenase / Q000235:genetics / Q000378:metabolism*
D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; C115441:Slc22a5 protein, rat; D000074058:Solute Carrier Family 22 Member 5; D050563:gamma-Butyrobetaine Dioxygenase; C023095:4-N-trimethylaminobutyraldehyde dehydrogenase; D000445:Aldehyde Oxidoreductases; D002331:Carnitine