The TRPC1 Ca2+-permeable channel inhibits exercise-induced protection against high-fat diet-induced obesity and type II diabetes

Krout, Danielle; Schaar, Anne; Sun, Yuyang; Sukumaran, Pramod; Roemmich, James N.; Singh, Brij B.; Larson, Kate

doi:10.1074/jbc.m117.809954

Cited by 33 publications

(34 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TRPC1, TRPC4, TRPC5, and TRPC6 have been reported to be expressed in both preadipocytes and adipocytes, suggesting that these TRPCs may participate in adipogenesis [87]. Indeed, it has been proved that TRPC1 negatively regulates HFD-treatment induced obesity [88]. Besides, TRPC4 and TRPC6 were differentially expressed in pre-adipocytes and mature adipocytes.…”

Section: Other Trp Members In Adipogenesismentioning

confidence: 99%

Involvement of calcium channels in the regulation of adipogenesis

Zhai

Yang

et al. 2020

Adipocyte

View full text Add to dashboard Cite

As an important second messenger in adipocytes, calcium ions (Ca 2+) are essential in regulating various intracellular signalling pathways that control critical cellular functions. Calcium channels show selective permeability to Ca 2+ and facilitate Ca 2+ entry into the cytoplasm, which are normally located in the plasmatic and intracellular membranes. The increase of cytosolic Ca 2+ modulates a variety of signalling pathways and results in the transcription of target genes that contribute to adipogenesis, a key cellular event includes proliferation and differentiation of adipocyte. In the past decades, the involvement of some Ca 2+-permeable ion channels, such as Ca 2+ release-activated Ca 2+ channels, transient receptor potential channels, voltage-gated calcium channels and others, in adipogenesis has been extensively explored. In the present review, we provided a summary of the expression and contributions of these Ca 2+-permeable channels in mediating Ca 2+ influxes that drive adipogenesis. Moreover, we discussed their potentials as future therapeutic targets.

show abstract

Section: Other Trp Members In Adipogenesismentioning

confidence: 99%

Involvement of calcium channels in the regulation of adipogenesis

Zhai

Yang

et al. 2020

Adipocyte

View full text Add to dashboard Cite

show abstract

“…Likewise, another recently identified small‐molecule blocker, AC1903, of the homomeric TRPC5 channels has been found to suppress progressive kidney diseases (Zhou et al, ). Another study recently suggested that Ca 2+ permeable channels containing TRPC1 block exercise‐induced protection against high‐fat diet‐induced obesity and type II diabetes suggesting that the TRPC1 plays an vital role in the regulation of adiposity (Krout et al, ).…”

Section: Introductionmentioning

confidence: 99%

Treasure troves of pharmacological tools to study transient receptor potential canonical 1/4/5 channels

Rubaiy

2019

British J Pharmacology

View full text Add to dashboard Cite

Canonical or classical transient receptor potential 4 and 5 proteins (TRPC4 and TRPC5) assemble as homomers or heteromerize with TRPC1 protein to form functional nonselective cationic channels with high calcium permeability. These channel complexes, TRPC1/4/5, are widely expressed in nervous and cardiovascular systems, also in other human tissues and cell types. It is debatable that TRPC1 protein is able to form a functional ion channel on its own. A recent explosion of molecular information about TRPC1/4/5 has emerged including knowledge of their distribution, function, and regulation suggesting these three members of the TRPC subfamily of TRP channels play crucial roles in human physiology and pathology. Therefore, these ion channels represent potential drug targets for cancer, epilepsy, anxiety, pain, and cardiac remodelling. In recent years, a number of highly selective small-molecule modulators of TRPC1/4/5 channels have been identified as being potent with improved pharmacological properties. This review will focus on recent remarkable small-molecule agonists: (−)-englerin A and tonantzitlolone and antagonists: Pico145 and HC7090, of TPRC1/4/5 channels. In addition, this work highlights other recently identified modulators of these channels such as the benzothiadiazine derivative, riluzole, ML204, clemizole, and AC1903. Together, these treasure troves of agonists and antagonists of TRPC1/4/5 channels provide valuable hints to comprehend the functional importance of these ion channels in native cells and in vivo animal models. Importantly, human diseases and disorders mediated by these proteins can be studied using these compounds to perhaps initiate drug discovery efforts to develop novel therapeutic agents.

show abstract

“…The TRPC1 promoter has 3 putative NF-κB binding sites. Previous studies have found that the binding site of NF-κB is lo- cated in the 5′ regulatory region of the TRPC1 promoter [39]. Overexpression of TRPC1 in neuroblastoma cells leads to increased NF-κB activity.…”

Section: Discussionmentioning

confidence: 99%

The Effect and Mechanism of TRPC1, 3, and 6 on the Proliferation, Migration, and Lumen Formation of Retinal Vascular Endothelial Cells Induced by High Glucose

et al. 2020

View full text Add to dashboard Cite

Objective: Transient receptor potential canonical (TRPC) channels are involved in neovascularization repairing after vascular injury in many tissues. However, whether TRPCs play a regulatory role in the development of diabetic retinopathy (DR) has rarely been reported. In the present study, we selected TRPC1, 3, and 6 to determine their roles and mechanism in human retina vascular endothelial cells (HREC) under high glucose (HG) conditions. Methods: HRECs were cultured in vitro under HG, hyper osmosis, and normal conditions. The expression of TRPC1, 3, and 6 in the cells at 24 and 48 h were detected by RT-polymerase chain reaction (PCR), Western blot and cell immunohistochemistry (IHC); In various concentrations, SKF96365 acted on HG cultured HRECs, the expression of vascular endothelial growth factor (VEGF) were detected by the same methods above; and the CCK-8, Transwell, cell scratch assay, and Matrigel assay were used to assess cell proliferation, migration, and lumen formation. Results: The RT-PCR, Western blot, and IHC results showed that TRPC1 expression was increased, and TRPC6 mRNA expression was increased under high-glucose conditions. SKF96365 acted on HG cultured HRECs that VEGF expression was significantly decreased. The CCK-8 assay, Transwell assay, cell scratch assay, and Matrigel assay showed that cell proliferation, migration, and lumen formation were downregulated by SKF96365. Conclusion: HG can induce increased expression of TRPC1 and 6 in HRECs. Inhibition of the TRPC pathway not only can decrease VEGF expression but also can prevent proliferation, migration, and lumen formation of HRECs induced by HG. Inhibition of TRPC channels is expected to become a drug target for

show abstract

The TRPC1 Ca2+-permeable channel inhibits exercise-induced protection against high-fat diet-induced obesity and type II diabetes

Cited by 33 publications

References 45 publications

Involvement of calcium channels in the regulation of adipogenesis

Involvement of calcium channels in the regulation of adipogenesis

Treasure troves of pharmacological tools to study transient receptor potential canonical 1/4/5 channels

The Effect and Mechanism of TRPC1, 3, and 6 on the Proliferation, Migration, and Lumen Formation of Retinal Vascular Endothelial Cells Induced by High Glucose

Contact Info

Product

Resources

About