Lactate: a pearl dropped in the ocean—an overlooked signal molecule in physiology and pathology

Wu, Yue; Ma, Wanqi; Liu, Wei; Zhang, Shuping

doi:10.1002/cbin.11975

Cited by 10 publications

(4 citation statements)

References 108 publications

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“…The hallmark of chronic wounds is matrix metalloproteinase (MMP) overactivity, the use of acidic wound dressings to shift from a high alkaline pH to a low alkaline pH in chronic wounds may reduce MMP activity and promote the transition from the inflammatory to the proliferative phase and angiogenesis (Trengove et al, 1999). Lactate, initially considered a metabolic waste product, has been studied and shown to regulate changes in the wound microenvironment thereby promoting wound healing (Wu et al, 2023). It has been reported that the accumulation of lactate in the organism reduces the pH of the alkaline environment caused by reduced carbon dioxide and elevated oxygen tension, allowing cells that favor wound healing to proliferate and differentiate within the appropriate physiological pH range (DeBerardinis & Chandel, 2020).…”

Section: Lactate In the Wound Microenvironmentmentioning

confidence: 99%

Mechanisms regulating wound healing: Functional changes in biology mediated by lactate and histone lactylation

Wu,

Liang,

Han

et al. 2023

Journal Cellular Physiology

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The high incidence, low healing rate and huge economic burden of wounds (especially chronic wounds) worldwide remain a great challenge for clinical staff and patients. The various stages of wound healing are regulated by paracrine or autocrine cytokines and growth factors, and the study of their intrinsic mechanisms is a prerequisite for better wound treatment. Lactate, the end product of glycolysis, plays a role in all stages of wound healing, and recent studies have identified lactate as an epigenetic regulator that regulates gene expression through histone lysine lactylation and stimulates posttranslational modifications to regulate related gene expression, thereby causing a series of biological functional changes. This article reviews the progress of research on lactate and lactylation during wound healing or in related diseases, including its involvement in immune regulation, inflammation control, and proliferative remodeling, and finally describes the prospects for lactate therapy regarding wound healing.

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Section: Lactate In the Wound Microenvironmentmentioning

confidence: 99%

Mechanisms regulating wound healing: Functional changes in biology mediated by lactate and histone lactylation

Wu,

Liang,

Han

et al. 2023

Journal Cellular Physiology

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“…We reasoned that the nanomicelles could circulate for a long period due to the improved stability, bulky size, and reduced immunogenicity, resulting in improved tumor accumulation. Since the tumor microenvironment is slightly acidic (extracellular pH: 6.4–7.1), the nanomicelles should dissociate into positively charged unimers to adsorb onto the tumor cell surface to trigger the transcytosis of CAT-PEPA, leading to enhanced tumor penetration and thus efficient hypoxia reversion.…”

Section: Introductionmentioning

confidence: 99%

“…Since the tumor microenvironment is slightly acidic (extracellular pH: 6.4−7.1), 30 the nanomicelles should dissociate into positively charged unimers to adsorb onto the tumor cell surface to trigger the transcytosis of CAT-PEPA, leading to enhanced tumor penetration and thus efficient hypoxia reversion.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Reversion by Low-Immunogenic Ultra-Acid-Sensitive Comicelles of Protein–Polymer Conjugates Sensitizes Tumors to Photodynamic Therapy

Huang,

Zhang,

Sun

et al. 2024

J. Am. Chem. Soc.

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Hypoxia is characteristic of the tumor microenvironment, which is correlated with resistance to photodynamic therapy (PDT), radiotherapy, chemotherapy, and immunotherapy. Catalase is potentially useful to catalyze the conversion of endogenous H 2 O 2 to O 2 for hypoxia reversion. However, the efficient delivery of catalase into the hypoxia regions of tumors is a huge challenge. Here, we report the self-assembly of ultra-acid-sensitive polymer conjugates of catalase and albumin into nanomicelles that are responsive to the acidic tumor microenvironment. The immunogenicity of catalase is mitigated by the presence of albumin, which reduces the cross-linking of catalase with B cell receptors, resulting in improved pharmacokinetics. The ultra acid sensitivity of the nanomicelles makes it possible to efficiently escape the lysosomal degradation after endocytosis and permeate into the interior of tumors to reverse hypoxia in vitro and in vivo. In mice bearing triplenegative breast cancer, the nanomicelles loaded with a photosensitizer effectively accumulate and penetrate into the whole tumors to generate a sufficient amount of O 2 to reverse hypoxia, leading to enhanced efficacy of PDT without detectable side effects. These findings provide a general strategy of self-assembly to design low-immunogenic ultra-acid-sensitive comicelles of protein−polymer conjugates to reverse tumor hypoxia, which sensitizes tumors to PDT.

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“…Over the last two decades there has been growing recognition that lactate, the end product of glycolysis, serves many functions, including acting as a source of energy, a signaling molecule, and even as an epigenetic regulator. The high metabolic demands of the brain and the numerous roles of lactate in CNS function have been extensively discussed elsewhere [5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Aging and memory are altered by genetically manipulating lactate dehydrogenase in the neurons or glia of flies

Frame

Robinson

Mahmoudzadeh

et al. 2023

Aging

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The astrocyte-neuron lactate shuttle hypothesis posits that glial-generated lactate is transported to neurons to fuel metabolic processes required for long-term memory. Although studies in vertebrates have revealed that lactate shuttling is important for cognitive function, it is uncertain if this form of metabolic coupling is conserved in invertebrates or is influenced by age. Lactate dehydrogenase (Ldh) is a rate limiting enzyme that interconverts lactate and pyruvate. Here we genetically manipulated expression of Drosophila melanogaster lactate dehydrogenase (dLdh) in neurons or glia to assess the impact of altered lactate metabolism on invertebrate aging and long-term courtship memory at different ages. We also assessed survival, negative geotaxis, brain neutral lipids (the core component of lipid droplets) and brain metabolites. Both upregulation and downregulation of dLdh in neurons resulted in decreased survival and memory impairment with age. Glial downregulation of dLdh expression caused age-related memory impairment without altering survival, while upregulated glial dLdh expression lowered survival without disrupting memory. Both neuronal and glial dLdh upregulation increased neutral lipid accumulation. We provide evidence that altered lactate metabolism with age affects the tricarboxylic acid (TCA) cycle, 2-hydroxyglutarate (2HG), and neutral lipid accumulation. Collectively, our findings indicate that the direct alteration of lactate metabolism in either glia or neurons affects memory and survival but only in an age-dependent manner.

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Lactate: a pearl dropped in the ocean—an overlooked signal molecule in physiology and pathology

Cited by 10 publications

References 108 publications

Mechanisms regulating wound healing: Functional changes in biology mediated by lactate and histone lactylation

Mechanisms regulating wound healing: Functional changes in biology mediated by lactate and histone lactylation

Hypoxia Reversion by Low-Immunogenic Ultra-Acid-Sensitive Comicelles of Protein–Polymer Conjugates Sensitizes Tumors to Photodynamic Therapy

Aging and memory are altered by genetically manipulating lactate dehydrogenase in the neurons or glia of flies

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