Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our laboratory has previously shown that the vacuolar H(+)-ATPase, located in a subpopulation of specialized cells establishes a luminal acidic environment in the epididymis and proximal part of the vas deferens (Breton S, Smith PJS, Lui B, and Brown D. Nat Med 2: 470-472, 1996). Low luminal pH is critical for sperm maturation and maintenance of sperm in a quiescent state during storage in these organs. In the present study we examined the regulation of proton secretion in the epididymis and vas deferens. In vivo microtubule disruption by colchicine induced an almost complete loss of H(+)-ATPase apical polarity. Endocytotic vesicles, visualized by Texas red-dextran internalization, contain H(+)-ATPase, indicating active endocytosis of the pump. Cellubrevin, an analog of the vesicle soluble N-ethyl malemide-sensitive factor attachment protein (SNAP) receptor (v-SNARE) synaptobrevin, is highly enriched in H(+)-ATPase-rich cells of the epididymis and vas deferens, and tetanus toxin treatment markedly inhibited bafilomycin-sensitive proton secretion by 64.3+/-9.0% in the proximal vas deferens. Western blotting showed effective cleavage of cellubrevin by tetanus toxin in intact vas deferens, demonstrating that the toxin gained access to cellubrevin. These results suggest that H(+)-ATPase is actively endocytosed and exocytosed in proton-secreting cells of the epididymis and vas deferens and that net proton secretion requires the participation of the v-SNARE cellubrevin.
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PMID:Tetanus toxin-mediated cleavage of cellubrevin inhibits proton secretion in the male reproductive tract. 1080 83

Brown adipose tissue (BAT) is considered of metabolic significance in mammalian physiology, because it plays an important role in regulating energy balance. Alterations in this tissue have been associated with obesity and type 2 diabetes. The molecular mechanisms modulating brown adipocyte differentiation are not fully understood. Using a murine brown preadipocyte cell line, primary cultures, and 3T3-L1 cells, we analyzed the contribution of various intracellular signaling pathways to adipogenic and thermogenic programs. Sequential activation of p38MAPK and LKB1-AMPK-tuberous sclerosis complex 2 (TSC2) as well as significant attenuation of ERK1/2 and mammalian target of rapamycin (mTOR)-p70 S6 kinase 1 (p70S6K1) activation was observed through the brown differentiation process. This study demonstrates a critical role for AMPK in controlling the mTOR-p70S6K1 signaling cascade in brown but not in 3T3-L1 adipocytes. We observed that mTOR activity is essential in the first stages of differentiation. Nevertheless, subsequent inhibition of this cascade by AMPK activation is also necessary at later stages. An in vivo study showed that prolonged 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR)-induced AMPK activation increases uncoupling protein 1 expression and induces an accumulation of brown adipocytes in white adipose tissue (WAT), as revealed by immunohistology. Moreover, the induction of brown adipogenesis in areas of white fat partially correlates with the body weight reduction detected in response to treatment with AICAR. Taken together, our study reveals that differentiation of brown adipocytes employs different signaling pathways from white adipocytes, with AMPK-mTOR cross talk a central mediator of this process. Promotion of BAT development in WAT by pharmacological activation of AMPK may have potential in treating obesity by acting on energy dissipation.
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PMID:Adenosine 5'-monophosphate-activated protein kinase-mammalian target of rapamycin cross talk regulates brown adipocyte differentiation. 2013 56