Effects of selective Bcl-2 inhibitor HA14-1 treatments on functional activity of magnocellular vasopressinergic neurons of rat hypothalamus.
In this study we examined whether in vivo treatments with Bcl-2 inhibitor HA14-1 can affect the function of vasopressinergic system of rat. HA14-1 is a novel organic compound that has micromolar affinity for Bcl-2 and Bcl-xL and acts as a mimetic of BH3-only proteins by antagonizing the anti-apoptotic Bcl-2 proteins and triggering Bax-dependent apoptosis. We found that intrahypothalamic injections of HA14-1 did not induce apoptosis of vasopressin (VP) cells of supraoptic nucleus, but led to activation of VP synthesis and release, resulting in decreased diuresis. Our data has also demonstrated that injections of HA14-1 increased phospho-MEK1/2, phospho-CREB and phospho-Elk-1 levels in magnocellular neurons. Thus we propose that injections of HA14-1 into the hypothalamus do not lead to neuronal death, but change the functional activity of VP neurons of hypothalamus centres.
Chernigovskaya
Elena V
EV
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Sankt-Petersburg, Russia.
Nikitina
Liubov S
LS
Dorofeeva
Nadezhda A
NA
Glazova
Margarita V
MV
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D048429:Cell Size; D004231:Diuresis / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014667:Vasopressins / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D001578:Benzopyrans; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; D014667:Vasopressins