Adenosine regulates Sertoli cell function by activating AMPK.
This work evaluates adenosine effects on Sertoli cell functions, which are different to those resulting from occupancy of purinergic receptors. The effects of adenosine and N(6)-cyclohexyladenosine (CHA) - an A(1) receptor agonist resistant to cellular uptake - on Sertoli cell physiology were compared. Adenosine but not CHA increased lactate production, glucose uptake, GLUT1, LDHA and MCT4 mRNA levels, and stabilized ZO-1 protein at the cell membrane. These differential effects suggested a mechanism of action of adenosine that cannot be solely explained by occupancy of type A(1) purinergic receptors. Activation by adenosine but not by CHA of AMPK was observed. AMPK participation in lactate production and ZO-1 stabilization was confirmed by utilizing specific inhibitors. Altogether, these results suggest that activation of AMPK by adenosine promotes lactate offer to germ cells and cooperates in the maintenance of junctional complex integrity, thus contributing to the preservation of an optimum microenvironment for a successful spermatogenesis.
Galardo
M N
MN
Centro de Investigaciones Endocrinológicas (CEDIE-CONICET), Hospital de Niños Ricardo Gutiérrez, Gallo 1330, C1425EDF Buenos Aires, Argentina.
Riera
M F
MF
Pellizzari
E H
EH
Sobarzo
C
C
Scarcelli
R
R
Denduchis
B
B
Lustig
L
L
Cigorraga
S B
SB
Meroni
S B
SB
D000091162:AMP-Activated Protein Kinase Kinases; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism; D007365:Intercellular Junctions / Q000187:drug effects / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D007773:Lactates / Q000378:metabolism; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000494:pharmacology; D012708:Sertoli Cells / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism
D051246:Glucose Transport Proteins, Facilitative; D007527:Isoenzymes; D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C027513:N(6)-cyclohexyladenosine; D004533:Egtazic Acid; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; C031143:AICA ribonucleotide; D005947:Glucose; D000241:Adenosine