Metabolic Stress Modulates Motor Patterning via AMP-Activated Protein Kinase

Rodgers-Garlick, C.; Armstrong, Gary A. B.; Robertson, R. Meldrum

doi:10.1523/jneurosci.5215-10.2011

Cited by 22 publications

(24 citation statements)

References 33 publications

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“…This response is consistent with previous studies on insects (Wegener, 1993;Weyel and Wegener, 1996;Campbell et al, 2018) and the stability of a low but non-zero ATP tissue concentration could indicate a regulated ATP homeostasis (Boutilier, 2001;Campbell et al, 2018). Entering coma when exposed to environmental stressors such as anoxia can in some respects be considered an adaptive mechanism as coma decreases energy demand (Rodgers-Garlick et al, 2011). Energy production of the hypometabolic L. migratoria is seemingly supported by anaerobic metabolism, as indicated by the hemolymph pH decrease of ∼0.8 units within the first 2 h of anoxia (Fig.…”

Section: Anoxia Causes Disruption Of Homeostasissupporting

confidence: 91%

Effects of anoxia on ATP, water, ion and pH balance in an insect (Locusta migratoria)

Ravn

Campbell

Gerber

et al. 2019

Journal of Experimental Biology

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When exposed to anoxia, insects rapidly go into a hypometabolic coma from which they can recover when exposed to normoxia again. However, prolonged anoxic bouts eventually lead to death in most insects, although some species are surprisingly tolerant. Anoxia challenges ATP, ion, pH and water homeostasis, but it is not clear how fast and to what degree each of these parameters is disrupted during anoxia, nor how quickly they recover. Further, it has not been investigated which disruptions are the primary source of the tissue damage that ultimately causes death. Here, we show, in the migratory locust (Locusta migratoria), that prolonged anoxic exposures are associated with increased recovery time, decreased survival, rapidly disrupted ATP and pH homeostasis and a slower disruption of ion ([K + ] and [Na + ]) and water balance. Locusts could not fully recover after 4 h of anoxia at 30°C, and at this point hemolymph [K + ] was elevated 5-fold and [Na + ] was decreased 2-fold, muscle [ATP] was decreased to ≤3% of normoxic values, hemolymph pH had dropped 0.8 units from 7.3 to 6.5, and hemolymph water content was halved. These physiological changes are associated with marked tissue damage in vivo and we show that the isolated and combined effects of hyperkalemia, acidosis and anoxia can all cause muscle tissue damage in vitro to equally large degrees. When locusts were returned to normoxia after a moderate (2 h) exposure of anoxia, ATP recovered rapidly (15 min) and this was quickly followed by recovery of ion balance (30 min), while pH recovery took 2-24 h. Recovery of [K + ] and [Na + ] coincided with the animals exiting the comatose state, but recovery to an upright position took ∼90 min and was not related to any of the physiological parameters examined.

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Section: Anoxia Causes Disruption Of Homeostasissupporting

confidence: 91%

Effects of anoxia on ATP, water, ion and pH balance in an insect (Locusta migratoria)

Ravn

Campbell

Gerber

et al. 2019

Journal of Experimental Biology

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“…In mammals [25] and locusts [21], [22], [26], [27] mimicking the effect of energetic compromise with the Na + /K + -ATPase inhibitor ouabain generates spontaneous SD similar to PID. To determine if a similar phenomenon could occur in the fly brain we exposed flies to volatilized ouabain (10 µl of 100 mM; see e.g [28]…”

Section: Resultsmentioning

confidence: 99%

Glial Hsp70 Protects K+ Homeostasis in the Drosophila Brain during Repetitive Anoxic Depolarization

et al. 2011

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Neural tissue is particularly vulnerable to metabolic stress and loss of ion homeostasis. Repetitive stress generally leads to more permanent dysfunction but the mechanisms underlying this progression are poorly understood. We investigated the effects of energetic compromise in Drosophila by targeting the Na+/K+-ATPase. Acute ouabain treatment of intact flies resulted in subsequent repetitive comas that led to death and were associated with transient loss of K+ homeostasis in the brain. Heat shock pre-conditioned flies were resistant to ouabain treatment. To control the timing of repeated loss of ion homeostasis we subjected flies to repetitive anoxia while recording extracellular [K+] in the brain. We show that targeted expression of the chaperone protein Hsp70 in glial cells delays a permanent loss of ion homeostasis associated with repetitive anoxic stress and suggest that this is a useful model for investigating molecular mechanisms of neuroprotection.

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“…It is reported that AMPK inhibition using compound C, a selective and ATP-competitive inhibitor of AMPK, reversed the effect of AICAR, an AMPK activator. 27,28) Our results showed that the phosphorylation of AMPK induced by AglRhz was inhibited by compound C (Fig. 2C), suggesting that AglRhz may exert its antitumor effect in HT-29 cells via AMPK activation.…”

Section: Discussionmentioning

confidence: 73%

Aglycon of Rhizochalin from the Rhizochalina incrustata Induces Apoptosis via Activation of AMP-Activated Protein Kinase in HT-29 Colon Cancer Cells

Khanal

Kang

Yun

et al. 2011

Biological & Pharmaceutical Bulletin

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Rhizocalin is the first two-headed sphingolipid like compound isolated from the sponge Rhizochalina incrustata.1) It has been shown that rhizochalin and its derivatives have antibacterial, selective DNA-damaging, antifungal and cytotoxic activity.1) In addition, accumulating evidence suggests that rhizochalin and its derivatives have potent antitumor activity in human cancer cell lines, including cervical cancer, leukemia, and colon cancer.2,3) However, the underlying mechanisms of its anticarcinogenic activity remain poorly understood.The AMP-activated protein kinase (AMPK), a serine/ theronine kinase present in all eukaryotes, is a sensor of cellular energy status. 4) Since tumor-suppressor genes such as TSC2 and LKB1 function as upstream kinases of AMPK, AMPK is known as an antiproliferative molecule. 5,6) Previous studies have reported that AMPK activators, 5-amino-4-imidazolecarboxamide riboside (AICAR) and metformin, inhibit the cell growth in cultured tumor cells and mouse xenograft models.6-8) AMPK activation also induces apoptosis in cancer cell lines such as neuroblastoma cells, pancreatic cells, glioma cells, and endometrial cancer cells. [9][10][11][12] In addition, AMPK activation by phytochemicals, such as quercetin and 24-hydroxyursolic acid, is involved in apoptosis in colon cancer cell lines 13,14) Therefore, AMPK activation by naturally occurring compounds has attractive potentials for cancer therapy.Here, we have investigated the role of aglycon of rhizochalin (AglRhz), two-headed sphingolipid-like compound isolated from the sponge Rhizochalina incrustata, in the activation of AMPK and induction of apoptosis in HT-29 colon cancer cells. We observed that AglRhz inhibited phosphorylation of p70S6K and its downstream target extracellular signal-regulated kinase (ERK) in a Raptor-dependent manner via AMPK activation. We have also found that AglRhz induced the cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP), as well as DNA fragmentation, resulting in the induction of apoptosis. In addition, AglRhz inhibited insulin-like growth factor (IGF)-induced cell neoplastic transformation in JB6 Cl41 cells and tumorigenicity in HT-29 cells. Taken together, our findings illustrate that AglRhz has a potent antitumor activity against the HT-29 colon cancer cells and suggests a molecular mechanism that underlies the antitumor activity of AglRhz. MATERIALS AND METHODS Reagents and AntibodiesMcCoy's 5A medium, L-glutamine, gentamicin, and fetal bovine serum (FBS) were purchased from Invitrogen (Carlsbad, CA, U.S.A.). Polyvinyl idene difluoride (PVDF) membrane was obtained from Millipore (Bedford, MA, U.S.A.). 3-[4,5-Dimethylthiazol-2-thiazoyl]-2,5-diphenyltetrazolium bromide (MTT) was from Sigma-Aldrich (St. Louis, MO, U.S.A.). Antibodies against phospho-p70S6K (Thr389), p70S6K, phospho-ERK1/2 (Thr202/Tyr204), ERK1/2, phospho-Raptor (Ser792), phospho-AMPK, cleaved caspase-3, cleaved PARP, caspase-3, and B-cell lymphoma 2 (Bcl-2) were from Cell Signaling Technology Inc. (Beverly, MA, U.S.A.); antibodies...

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Metabolic Stress Modulates Motor Patterning via AMP-Activated Protein Kinase

Cited by 22 publications

References 33 publications

Effects of anoxia on ATP, water, ion and pH balance in an insect (Locusta migratoria)

Effects of anoxia on ATP, water, ion and pH balance in an insect (Locusta migratoria)

Glial Hsp70 Protects K+ Homeostasis in the Drosophila Brain during Repetitive Anoxic Depolarization

Aglycon of Rhizochalin from the Rhizochalina incrustata Induces Apoptosis via Activation of AMP-Activated Protein Kinase in HT-29 Colon Cancer Cells

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