生命科学科研大百科

Glutamine metabolism is a pivotal process in cellular physiological activities, closely linked to tumor growth, energy homeostasis, and disease pathogenesis. This paper focuses on key molecules in the glutamine metabolic pathway, including the glutamine transporter ASCT2 (SLC1A5), rate-limiting enzymes GFAT1/GFAT2, glutaminases GLS1/GLS2, glutamate dehydrogenase, GOT1, and ASNS. It elaborates on their biological functions, catalytic mechanisms, and regulatory roles in processes such as hexosamine biosynthesis, glutaminolysis, and redox balance. In addition, the correlation between abnormal expression of these molecules and diseases such as cancer, hyperglycemia, and insulin resistance is discussed. Relevant antibodies for experimental research are listed to provide a theoretical reference and experimental tool support for the study of glutamine metabolism and its targeted therapy.

Stimulator of interferon genes (STING, TMEM173, MITA) is a transmembrane adaptor protein that is a critical component of the cellular innate immune response to pathogenic cytoplasmic DNA (1,2). STING is a ubiquitously expressed protein found predominantly in the ER (1). The enzyme cGAMP synthase (cGAS) produces the second messenger cyclic-GMP-AMP (cGAMP) in response to cytoplasmic DNA (3,4).

Alzheimer's Disease (AD) is one of the most common neurodegenerative diseases worldwide. Clinically, it is characterized by the presence of extracellular amyloid plaques and intracellular neurofibrillary tangles, resulting in neuronal dysfunction and cell death.

Macrophages are myeloid cells of the innate immune system that are found in all human tissues in the body and exhibit anatomical and functional diversity. These heterogenous cells are derived from monocyte precursors in the blood that infiltrate into the tissues and differentiate in the presence of cytokines and growth factors.

Interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) are pro-inflammatory cytokines (1). IL-1α is produced by many cell types, including epithelial cells, monocytes, and macrophages (1,2). It is typically sequestered but can be released during necroptosis or inflammasome activation (3-5). IL-1α is active in both its uncleaved (pro-IL-1α) and cleaved forms and thus acts as an alarmin, initiating signaling through IL-1R1 (6). IL-1β is not active until it is cleaved (7,8). IL-1β expression is induced by inflammatory stimuli, including TLR ligands, IL-1β itself, and tumor necrosis factor-alpha (TNF-α) (1,9,10). IL-1β is primarily synthesized by activated monocytes and macrophages. It activates innate immune cells and polarizes CD4+ T cells toward T helper (Th) 1 and Th17 cells (10).

Exosomes are small (30-150 nm) membrane-bound vesicles that are secreted by various cell types under normal and pathological conditions (1,2). They originate from intracellular multivesicular endosomes upon fusion with the plasma membrane. Exosomes have emerged as an important mechanism of intercellular communication facilitating the transfer of membrane and cytosolic proteins, lipids, and RNA.

Cluster of Differentiation 3 (CD3) is a multiunit protein complex expressed on the surface of T cells that directly associates with the T cell receptor (TCR). CD3 is composed of four polypeptides: ζ, γ, ε and δ. Engagement of the TCR complex with antigens presented in Major Histocompatibility Complexes (MHC) induces tyrosine phosphorylation in the immunoreceptor tyrosine-based activation motif (ITAM) of CD3 proteins.

Cluster of Differentiation 3 (CD3) is a multiunit protein complex expressed on the surface of T cells that directly associates with the T cell receptor (TCR). CD3 is composed of four polypeptides: ζ, γ, ε, and δ. Engagement of the TCR complex with antigens presented in major histocompatibility complexes induces tyrosine phosphorylation in the immunoreceptor tyrosine-based activation motif (ITAM) of CD3 proteins. CD3 phosphorylation is required for downstream signaling through ZAP-70 and p85 subunit of PI-3 kinase, leading to T cell activation, proliferation, and effector functions (1).

Heat shock protein (HSP) 27 is one of the small HSPs that are constitutively expressed at different levels in various cell types and tissues. Like other small HSPs, HSP27 is regulated at both the transcriptional and posttranslational levels (1). In response to stress, the HSP27 expression increases several-fold to confer cellular resistance to the adverse environmental change. HSP27 is phosphorylated at Ser15, Ser78, and Ser82 by MAPKAPK-2 as a result of the activation of the p38 MAP kinase pathway (2,3). Phosphorylation of HSP27 causes a change in its tertiary structure, which shifts from large homotypic multimers to dimers and monomers (4). It has been shown that phosphorylation and increased concentration of HSP27 modulates actin polymerization and reorganization (5,6).

MAPK Family; MAPKKK; MAPKK