Ca2+/Calmodulin-Dependent Protein Kinase Kinase Is Not Involved in Hypothalamic AMP-Activated Protein Kinase Activation by Neuroglucopenia

被引:9
|
作者
Kawashima, Junji
Alquier, Thierry
Tsuji, Youki
Peroni, Odile D.
Kahn, Barbara B.
机构
[1] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA
[2] Harvard Univ, Sch Med, Boston, MA USA
来源
PLOS ONE | 2012年 / 7卷 / 05期
基金
美国国家卫生研究院;
关键词
ALPHA-LIPOIC ACID; UPSTREAM KINASE; GLUCOSE-UPTAKE; CELLS; BETA; HYPOGLYCEMIA; RESPONSES;
D O I
10.1371/journal.pone.0036335
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hypoglycemia and neuroglucopenia stimulate AMP-activated protein kinase (AMPK) activity in the hypothalamus and this plays an important role in the counterregulatory responses, i.e. increased food intake and secretion of glucagon, corticosterone and catecholamines. Several upstream kinases that activate AMPK have been identified including Ca2+/Calmodulin-dependent protein kinase kinase (CaMKK), which is highly expressed in neurons. However, the involvement of CaMKK in neuroglucopenia-induced activation of AMPK in the hypothalamus has not been tested. To determine whether neuroglucopenia-induced AMPK activation is mediated by CaMKK, we tested whether STO-609 (STO), a CaMKK inhibitor, would block the effects of 2-deoxy-D-glucose (2DG)-induced neuroglucopenia both ex vivo on brain sections and in vivo. Preincubation of rat brain sections with STO blocked KCl-induced alpha 1 and alpha 2-AMPK activation but did not affect AMPK activation by 2DG in the medio-basal hypothalamus. To confirm these findings in vivo, STO was pre-administrated intracerebroventricularly (ICV) in rats 30 min before 2DG ICV injection (40 mu mol) to induce neuroglucopenia. 2DG-induced neuroglucopenia lead to a significant increase in glycemia and food intake compared to saline-injected control rats. ICV pre-administration of STO (5, 20 or 50 nmol) did not affect 2DG-induced hyperglycemia and food intake. Importantly, activation of hypothalamic alpha 1 and alpha 2-AMPK by 2DG was not affected by ICV pre-administration of STO. In conclusion, activation of hypothalamic AMPK by 2DG-induced neuroglucopenia is not mediated by CaMKK.
引用
收藏
页数:7
相关论文
共 50 条
  • [31] Regulation of multifunctional Ca2+/calmodulin-dependent protein kinases by Ca2+/calmodulin-dependent protein kinase phosphatase
    Ishida, A
    Okuno, S
    Kitani, T
    Kameshita, I
    Fujisawa, H
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 253 (01) : 159 - 163
  • [32] MULTIFUNCTIONAL CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE
    SCHULMAN, H
    HANSON, PI
    NEUROCHEMICAL RESEARCH, 1993, 18 (01) : 65 - 77
  • [33] Adiponectin Activates AMP-activated Protein Kinase in Muscle Cells via APPL1/LKB1-dependent and Phospholipase C/Ca2+/Ca2+/Calmodulin-dependent Protein Kinase Kinase-dependent Pathways
    Zhou, Lijun
    Deepa, Sathyaseelan S.
    Etzler, Julie C.
    Ryu, Jiyoon
    Mao, Xuming
    Fang, Qichen
    Liu, Dianna D.
    Torres, Jesus M.
    Jia, Weiping
    Lechleiter, James D.
    Liu, Feng
    Dong, Lily Q.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (33) : 22426 - 22435
  • [34] Generation of Autonomous Activity of Ca2+/Calmodulin-Dependent Protein Kinase Kinase β by Autophosphorylation
    Tokumitsu, Hiroshi
    Hatano, Naoya
    Fujimoto, Tomohito
    Yurimoto, Said
    Kobayashi, Ryoji
    BIOCHEMISTRY, 2011, 50 (38) : 8193 - 8201
  • [35] Studies on the substrate specificity of Ca2+/calmodulin-dependent protein kinase kinase alpha
    Okuno, S
    Kitani, T
    Fujisawa, H
    JOURNAL OF BIOCHEMISTRY, 1997, 122 (02): : 337 - 343
  • [36] Differential regulatory mechanism of Ca2+/calmodulin-dependent protein kinase kinase isoforms
    Tokumitsu, H
    Iwabu, M
    Ishikawa, Y
    Kobayashi, R
    BIOCHEMISTRY, 2001, 40 (46) : 13925 - 13932
  • [37] Role of Ca2+/Calmodulin-Dependent Protein Kinase Kinase in Adrenal Aldosterone Production
    Nanba, Kazutaka
    Chen, Andrew
    Nishimoto, Koshiro
    Rainey, William E.
    ENDOCRINOLOGY, 2015, 156 (05) : 1750 - 1756
  • [38] Ca2+/Calmodulin-Dependent Kinase (CaMK) Signaling via CaMKI and AMP-Activated Protein Kinase Contributes to the Regulation of WIPI-1 at the Onset of Autophagy
    Pfisterer, Simon G.
    Mauthe, Mario
    Codogno, Patrice
    Proikas-Cezanne, Tassula
    MOLECULAR PHARMACOLOGY, 2011, 80 (06) : 1066 - 1075
  • [39] Inhibition of the Ca2+/calmodulin-dependent protein kinase I cascade by cAMP-dependent protein kinase
    Matsushita, M
    Nairn, AC
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (15) : 10086 - 10093
  • [40] CHARACTERIZATION OF A CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE CASCADE - MOLECULAR-CLONING AND EXPRESSION OF CALCIUM/CALMODULIN-DEPENDENT PROTEIN-KINASE KINASE
    TOKUMITSU, H
    ENSLEN, H
    SODERLING, TR
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (33) : 19320 - 19324