Calcium Signaling Pathways: Key Pathways in the Regulation of Obesity

Song, Ziguo; Wang, Yu; Zhang, Fei; Yao, Fangyao; Sun, Chao

doi:10.3390/ijms20112768

Cited by 58 publications

(41 citation statements)

References 165 publications

(184 reference statements)

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“…The MAPK pathways have been demonstrated to serve an important role in the regulation of many cell biological behaviors, such as cell proliferation and cell apoptosis (25). An increase in cytoplasmic Ca 2+ levels activates the MAPK cascade (26,27). Three distinct groups of MAPKs, including ERK1/2, JNK, and p38 MAPK, are important for cancer cell apoptosis (28).…”

Section: Discussionmentioning

confidence: 99%

Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer

Kong

Shao

et al. 2019

Oncol Rep

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Endometrial cancer (EC) is one of the most common malignant gynecological tumors in women. The main treatments for EC (surgery, chemotherapy and radiation therapy) produce significant side effects. Thus, it is urgent to identify promising therapeutic targets and prognostic markers. CACNA2D3, as a member of the calcium channel regulatory α2δ subunit family, is reported to exert a tumor suppressive effect in numerous cancers. However, the function of CACNA2D3 in EC is not well known. In the present study, CACNA2D3 was lowly expressed in EC tissues and cells. The overexpression of CACNA2D3 via lentiviral particle injection significantly blocked the tumor growth in an in vivo xenograft model. In vitro, the overexpression of CACNA2D3 markedly inhibited cell proliferation and migration, and promoted cell apoptosis and calcium influx. These data revealed that CACNA2D3 functions as a tumor suppressor in EC. It was also revealed that the addition of progesterone (P4) blocked tumor growth in Ishikawa-injected nude mice. P4 induced the expression of CACNA2D3 in vivo and in vitro, and the silencing of CACNA2D3 affected P4-inhibited cell proliferation and P4-induced cell apoptosis and calcium influx. In Ishikawa cells, P4 enhanced the expression of phosphorylated (p)-p38 MAPK and PTEN, but blocked the levels of p-PI3K and p-AKT. The knockdown of CACNA2D3 blocked the function of P4. These data revealed that P4 promoted cell apoptosis via the activation of the CACNA2D3/Ca2+/p38 MAPK pathway, and blocked cell proliferation via suppression of the PI3K/AKT pathway. Collectively, these findings indicated the antitumor role of CACNA2D3 in EC, and revealed the mechanism of P4 inhibition of EC progression, which provided a new target for EC therapy and new evidence for P4 in EC therapy.

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Section: Discussionmentioning

confidence: 99%

Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer

Kong

Shao

et al. 2019

Oncol Rep

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“…The fat cell differentiation or adipocyte formation plays a crucial role in adipogenesis during obesity [46]. Calcium is an important ion for normal physiological functioning and calcium ion binding is involved in calcium signaling pathways which have been shown as key pathways in the regulation of obesity in many studies [40][41][42]57]. The multiple calcium signaling pathways play a most important role in the biological clock, neuronal excitability, and intestinal microbial activity for regulating the food intake and adipocyte metabolism, which subsequently reduces the occurrence of obesity [57].…”

Section: Other Enriched Gene Ontology Termsmentioning

confidence: 99%

“…Calcium is an important ion for normal physiological functioning and calcium ion binding is involved in calcium signaling pathways which have been shown as key pathways in the regulation of obesity in many studies [40][41][42]57]. The multiple calcium signaling pathways play a most important role in the biological clock, neuronal excitability, and intestinal microbial activity for regulating the food intake and adipocyte metabolism, which subsequently reduces the occurrence of obesity [57]. The genes enriched included CACNA1B, which also harbored the significantly associated SNP BICF2P116826, encoding calcium voltage-gated channel subunit alpha1 B, which is associated with adipogenesis [40][41][42] and most importantly, it was identified as a candidate gene for body weight trait in our association study.…”

Section: Other Enriched Gene Ontology Termsmentioning

confidence: 99%

Identification of Candidate Genes and Pathways Associated with Obesity-Related Traits in Canines via Gene-Set Enrichment and Pathway-Based GWAS Analysis

Sheet

Srikanth

Cha

et al. 2020

Animals

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The present study aimed to identify causative loci and genes enriched in pathways associated with canine obesity using a genome-wide association study (GWAS). The GWAS was first performed to identify candidate single-nucleotide polymorphisms (SNPs) associated with obesity and obesity-related traits including body weight and blood sugar in 18 different breeds of 153 dogs. A total of 10 and 2 SNPs were found to be significantly (p < 3.74 × 10−7) associated with body weight and blood sugar, respectively. None of the SNPs were identified to be significantly associated with obesity trait. We subsequently followed up the GWAS analysis with gene-set enrichment and pathway analyses. A gene-set with 1057, 1409, and 1243 SNPs annotated to 449, 933 and 820 genes for obesity, body weight, and blood sugar, respectively was created by sub-setting the GWAS result at a threshold of p < 0.01 for the gene-set enrichment analysis. In total, 84 GO and 21 KEGG pathways for obesity, 114 GO and 44 KEGG pathways for blood sugar, 120 GO and 24 KEGG pathways for body weight were found to be enriched. Among the pathways and GO terms, we highlighted five enriched pathways (Wnt signaling pathway, adherens junction, pathways in cancer, axon guidance, and insulin secretion) and seven GO terms (fat cell differentiation, calcium ion binding, cytoplasm, nucleus, phospholipid transport, central nervous system development, and cell surface) that were found to be shared among all the traits. Our data provide insights into the genes and pathways associated with obesity and obesity-related traits.

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“…The FY-associated SNP on chromosome X was located nearby the GRPR , this gene is gastrin releasing peptide receptor, gastrin-releasing peptide regulates numerous functions of gastrointestinal and central nervous system, which involved in calcium signaling pathway and neuroactive ligand-receptor interaction. Song reviewed a lot of studies on calcium signaling pathway participated in the effect of the sympathetic never in regulating adipose metabolism [39]. We suspect that GRPR gene may affect milk fat through the calcium signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Ten Genetic Loci Identified for Milk Yield, Fat, and Protein in Holstein Cattle

Liu

Zhou

Chen

et al. 2020

Preprint

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The production of high-yield and high-quality milk is the direct economic goals of dairy industry breeding. Understanding the genetic architecture underlying milk-related traits is beneficial so that genetic variants can be targeted toward the overall improvement. In this study, we measured five traits related to milk production and components in Holstein cattle population from China.These traits included milk yield, protein yield, and fat yields; fat percentage and protein percentages. We used the estimated breeding values as dependent variables to conduct the genome-wide association study (GWAS). Breeding values were estimated through pedigree relationships by using a mixed linear model for individuals with and without phenotypic data.Genotyping was carried out on the individuals with phenotypes by using the Illumina BovineSNP150 BeadChip. The association analyses were conducted by using the Fixed and random model Circulating Probability Unification (FarmCPU) method. A total of 10 SNPs was detected above the genome-wide significant threshold, six were located in previously reported QTL regions. We also found 8 candidate genes each is within a distance of 120 kb upstream and downstream to an associated SNPs, the most significant SNP affecting milk fat and protein percentage is in the DGAT1 gene. These genetic variants and potential candidate genes would be valuable resources to enhance dairy cattle breeding.

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Calcium Signaling Pathways: Key Pathways in the Regulation of Obesity

Cited by 58 publications

References 165 publications

Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer

Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer

Identification of Candidate Genes and Pathways Associated with Obesity-Related Traits in Canines via Gene-Set Enrichment and Pathway-Based GWAS Analysis

Ten Genetic Loci Identified for Milk Yield, Fat, and Protein in Holstein Cattle

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