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Published on: December 23, 2018
KRAS Affects the Lipid Composition by Regulating Mitochondrial Functions and MAPK Activation in Bovine Mammary
Wenjie Yu1, Hao Jiang1,2, Fengjiao Liu1
1Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China.
Abstract:
Kirsten rat sarcoma viral oncogene homolog (KRAS), or guanosine triphosphatase KRAS, is a proto-oncogene that encodes the small guanosine triphosphatase transductor protein. Previous studies have found that KRAS can promote cytokine secretion, cell chemotaxis, and survival. However, its effects on milk fat synthesis in bovine mammary epithelial cells are unclear. In this study, the effects of KRAS inhibition on cell metabolism, autophagy, oxidative stress, endoplasmic reticulum stress, mitochondrial function, and lipid composition as well as the potential mechanisms were detected in an immortalized dairy cow mammary epithelial cell line (MAC-T). The results showed that inhibition of KRAS changed the lipid composition (especially the triglyceride level), mitochondrial functions, autophagy, and endoplasmic reticulum stress in cells. Moreover, KRAS inhibition regulated the levels of the mammalian target of rapamycin and mitogen-activated protein kinase (extracellular regulated protein kinases, c-Jun N-terminal kinases, p38) activation. These results indicated that regulation of KRAS would affect the synthesis and composition of milk fat. These results are also helpful for exploring the synthesis and secretion of milk fat at the molecular level and provide a theoretical basis for improving the percentage of fat in milk and the yield of milk from cows.
Insights
Inhibition of Kirsten rat sarcoma viral oncogene homolog (KRAS) impacts bovine mammary cell lipid composition and mitochondrial function. This research offers insights into milk fat synthesis and secretion at a molecular level.
Area of Science:
- Molecular Biology
- Cellular Metabolism
- Dairy Science
Background:
- Kirsten rat sarcoma viral oncogene homolog (KRAS) is a proto-oncogene involved in cell signaling.
- KRAS's role in milk fat synthesis in bovine mammary epithelial cells is not well understood.
- Previous research links KRAS to cytokine secretion, cell chemotaxis, and survival.
Purpose of the Study:
- To investigate the effects of KRAS inhibition on bovine mammary epithelial cells (MAC-T).
- To determine KRAS's influence on cell metabolism, autophagy, oxidative stress, ER stress, mitochondrial function, and lipid composition.
- To elucidate the molecular mechanisms underlying KRAS's role in milk fat synthesis.
Main Methods:
- Utilized an immortalized dairy cow mammary epithelial cell line (MAC-T).
- Inhibited KRAS expression to observe cellular changes.
- Analyzed effects on cell metabolism, autophagy, oxidative stress, endoplasmic reticulum stress, mitochondrial function, and lipid composition.
Main Results:
- KRAS inhibition altered lipid composition, particularly triglyceride levels, in MAC-T cells.
- Observed changes in mitochondrial function, autophagy, and endoplasmic reticulum stress following KRAS inhibition.
- KRAS inhibition modulated the activation of mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) pathways.
Conclusions:
- Regulation of KRAS significantly affects milk fat synthesis and composition in bovine mammary cells.
- Findings provide a molecular understanding of milk fat production and secretion.
- Results offer a theoretical basis for improving milk fat percentage and yield in dairy cows.
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