Placental malnutrition changes the regulatory network of renal Na-ATPase in adult rat progeny: Reprogramming by maternal α-tocopherol during lactation.
Prenatal malnutrition is responsible for the onset of alterations in renal Na(+) transport in the adult offspring. Here we investigated the molecular mechanisms by which increased formation of reactive oxygen species during prenatal malnutrition affects the pathways that couple angiotensin II (Ang II) receptors (AT(1)R and AT(2)R) to kidney Na(+)-ATPase in adulthood, and how maternal treatment with α-tocopherol can prevent alterations in the main regulatory cascade of the pump. The experiments were carried out on the adult progeny of control and malnourished dams during pregnancy that did or did not receive α-tocopherol during lactation. Malnutrition during pregnancy increased maternal hepatic and adult offspring renal malondialdehyde levels, which returned to control after supplementation with α-tocopherol. In the adult offspring, placental malnutrition programmed: decrease in Na(+)-ATPase activity, loss of the physiological stimulation of this pump by Ang II, up-regulation of AT(1)R and AT(2)R, decrease in membrane PKC activity, selective decrease of the PKCε isoform expression, and increase in PKA activity with no change in PKA α-catalytic subunit expression. These alterations were reprogrammed to normal levels by α-tocopherol during lactation. The influence of α-tocopherol on the signaling machinery in adult offspring indicates selective non-antioxidant effects at the gene transcription and protein synthesis levels.
Vieira-Filho
Leucio D
LD
Department of Physiology and Pharmacology, Center of Biological Sciences, Federal University of Pernambuco, Recife, Brazil; National Institute of Science and Technology for Structural Biology and Bioimaging, Rio de Janeiro, Brazil.
Lara
Lucienne S
LS
Silva
Paulo A
PA
Santos
Felipe T J
FT
Luzardo
Ricardo
R
Oliveira
Fabiana S T
FS
Paixão
Ana D O
AD
Vieyra
Adalberto
A
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000201:enzymology* / Q000378:metabolism; D007774:Lactation; D044342:Malnutrition / Q000150:complications* / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000627:therapeutic use*
D027682:Cation Transport Proteins; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase; D024502:alpha-Tocopherol