Activation of AMPK by chitosan oligosaccharide in intestinal epithelial cells: Mechanism of action and potential applications in intestinal disorders

Muanprasat, Chatchai; Wongkrasant, Preedajit; Satitsri, Saravut; Moonwiriyakit, Aekkacha; Pongkorpsakol, Pawin; Mattaveewong, Tharinee; Pichyangkura, Rath; Chatsudthipong, Varanuj

doi:10.1016/j.bcp.2015.05.016

Cited by 116 publications

(103 citation statements)

References 40 publications

(51 reference statements)

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“…Although we cannot rule out the actions of the drug on the CaSRs on the cell surface, the ability of the drug to mimic the actions of TG and free extracellular Ca to block FFSS-induced chondrocyte terminal differentiation supports its direct action on ER CaSR. In supporting this idea, Muanprasat (46) reported that NPS2143 acts through ER CaSR to suppress a Chitosan oligosaccharide-induced increase in [Ca 2þ ].…”

Section: Discussionmentioning

confidence: 92%

Prevention of Injury-Induced Osteoarthritis in Rodent Temporomandibular Joint by Targeting Chondrocyte CaSR

Zhang

Yang

Wan

et al. 2018

Journal of Bone and Mineral Research

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Traumatic joint injuries produce osteoarthritic cartilage manifesting accelerated chondrocyte terminal differentiation and matrix degradation via unknown cellular and molecular mechanisms. Here we report the ability of biomechanical stress to increase expression of the calcium‐sensing receptor (CaSR), a pivotal driver of chondrocyte terminal differentiation, in cultured chondrogenic cells subjected to fluid flow shear stress (FFSS) and in chondrocytes of rodent temporomandibular joint (TMJ) cartilage subjected to unilateral anterior cross‐bite (UAC). In cultured ATDC5 cells or TMJ chondrocytes, FFSS induced Ca2+ loading and CaSR localization in endoplasmic reticulum (ER), casually accelerating cell differentiation that could be abrogated by emptying ER Ca2+ stores or CaSR knockdown. Likewise, acute chondrocyte‐specific Casr knockout (KO) prevented the UAC‐induced acceleration of chondrocyte terminal differentiation and matrix degradation in TMJ cartilage in mice. More importantly, local injections of CaSR antagonist, NPS2143, replicated the effects of Casr KO in preventing the development of osteoarthritic phenotypes in TMJ cartilage of the UAC‐treated rats. Our study revealed a novel pathological action of CaSR in development of osteoarthritic cartilage due to aberrant mechanical stimuli and supports a therapeutic potential of calcilytics in preventing osteoarthritis in temporomandibular joints by targeting the CaSR. © 2018 American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 92%

Prevention of Injury-Induced Osteoarthritis in Rodent Temporomandibular Joint by Targeting Chondrocyte CaSR

Zhang

Yang

Wan

et al. 2018

Journal of Bone and Mineral Research

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“…27 Either chitosan oligosaccharides or flufenamic acid can promote TJ reassembly following Ca 2+ switch and increase TEER in T84 cells in an AMPK-dependent manner, since co-incubation of either chitosan oligosaccharides or flufenamic acid with Compound C abolishes their beneficial effects on TJ assembly. 79,80 Though the mechanism leading to AMPKinduced TJ assembly remains elusive, it might be regulated partially through direct phosphorylation of TJ proteins and associated proteins. AMPK phosphorylates claudin 1 at Thr191 that promotes the formation of TJs in EpH4 breast cells.…”

Section: Ampk In Tight Junction Formation and Assemblymentioning

confidence: 99%

AMPK in regulation of apical junctions and barrier function of intestinal epithelium

Zhu

Sun

2018

Tissue Barriers

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Gut epithelium covers the inner layer of the gastrointestinal tract and provides a physical barrier to separate the host from its external environment, and its barrier function is critical for maintaining host health. AMP-activated protein kinase (AMPK) as a master regulator of energy metabolism plays a critical role in epithelial barrier function. AMPK activation promotes epithelial differentiation and facilitates cell polarity establishment, both of which strengthen epithelial barrier. In addition, AMPK promotes the assembly of tight junctions and adherens junctions by direct phosphorylation of proteins composing apical junctions, junctional anchors, and cytoskeletons. Pharmacological and nutraceutical compounds, as well as physiological states triggering AMPK activation strengthen epithelial barrier function. This review summarized recent progress in delineating the regulatory roles of AMPK in apical junction formation and barrier function of intestinal epithelium.

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“…Since therapeutic actions of TZDs in vivo are mediated by increased AMPK activity in muscle, liver, and adipose tissue , it is possible that a mode of action of GO2KA1 may involve AMP‐activated protein kinase (AMPK). Although high molecular weight chitosan and chitosan oligosaccharide are shown to increase AMPK activity in adipose tissue and intestinal epithelial cells, respectively , further studies are required to elucidate the precise mechanisms of action of low molecular weight GO2KA1. Given the complexity of blood glucose regulation, it is also necessary to identify the in vivo effects that GO2KA1 has on glucose and lipid metabolism in different tissues including skeletal muscle, liver and pancreas using different preclinical animal models.…”

Section: Discussionmentioning

confidence: 99%

Antidiabetic effect of chitosan oligosaccharide (GO2KA1) is mediated via inhibition of intestinal alpha‐glucosidase and glucose transporters and PPARγ expression

Kwon

Lee

et al. 2016

BioFactors

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We have previously reported that administration of low molecular weight chitosan oligosaccharide (GO2KA1) significantly suppressed postprandial blood glucose rise with increased plasma adiponectin and HbA1c levels in animals and humans. However, the cellular mechanisms whereby GO2KA1 exerts antihyperglycemic effects still remain to be determined. Using intestinal Caco-2 cells and 3T3-L1 cells, here we show that GO2KA1 has dual modes of antidiabetic action by (1) inhibiting intestinal α-glucosidase as well as glucose transporters SGLT1 and GLUT2 that were distinct from the acarbose effect; (2) enhancing adipocyte differentiation, PPARγ expression and its target genes, such as FABP4, adiponectin, and GLUT4, whereas the effects were abolished by co-treatment with BADGE, a PPARγ antagonist. Moreover, GO2KA1 significantly increased glucose uptake, which was reduced in the presence of BADGE. Our data show that GO2KA1 may prevent hyperglycemia by inhibiting intestinal glucose digestion and transport and also enhance glucose uptake, at least in part, by upregulating adiponectin expression through PPARγ in adipocytes. These findings may provide potential molecular modes of action for the antidiabetic effects of chitosan oligosaccharide observed in clinical and animal studies. © 2016 BioFactors, 43(1):90-99, 2017.

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Activation of AMPK by chitosan oligosaccharide in intestinal epithelial cells: Mechanism of action and potential applications in intestinal disorders

Cited by 116 publications

References 40 publications

Prevention of Injury-Induced Osteoarthritis in Rodent Temporomandibular Joint by Targeting Chondrocyte CaSR

Prevention of Injury-Induced Osteoarthritis in Rodent Temporomandibular Joint by Targeting Chondrocyte CaSR

AMPK in regulation of apical junctions and barrier function of intestinal epithelium

Antidiabetic effect of chitosan oligosaccharide (GO2KA1) is mediated via inhibition of intestinal alpha‐glucosidase and glucose transporters and PPARγ expression

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