HIF-1α regulates mTOR signaling pathway during salivary gland development

Kimura, Tomomasa; Sakai, Manabu; Gojo, Nao; Watanabe, Mikio; Uzawa, Narikazu; Sakai, Takayoshi

doi:10.1016/j.bbrc.2022.09.078

Cited by 2 publications

(2 citation statements)

References 25 publications

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“…For instance, it was shown that at the beginning of pregnancy, in physiological hypoxia, HIF-1α may act through the PI3K/Akt pathway promoting cell survival, while during prolonged ischemia, the same relationship may induce cell death [ 96 ]. Also, HIF-1α was found to have a strong relationship with the mTOR signaling pathway, which influenced embryonic organ development [ 97 ]. According to Kimura et al, HIF-1α negatively regulates the mTOR axis and suppresses salivary gland development under 1% O 2 .…”

Section: Chromogranin a Derivative: Catestatinmentioning

confidence: 99%

The Role of Catestatin in Preeclampsia

Bralewska,

Pietrucha,

Sakowicz

2024

IJMS

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Preeclampsia (PE) is a unique pregnancy disorder affecting women across the world. It is characterized by the new onset of hypertension with coexisting end-organ damage. Although the disease has been known for centuries, its exact pathophysiology and, most importantly, its prevention remain elusive. The basis of its associated molecular changes has been attributed to the placenta and the hormones regulating its function. One such hormone is chromogranin A (CgA). In the placenta, CgA is cleaved to form a variety of biologically active peptides, including catestatin (CST), known inter alia for its vasodilatory effects. Recent studies indicate that the CST protein level is diminished both in patients with hypertension and those with PE. Therefore, the aim of the present paper is to review the most recent and most relevant in vitro, in vivo, and clinical studies to provide an overview of the proposed impact of CST on the molecular processes of PE and to consider the possibilities for future experiments in this area.

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Section: Chromogranin a Derivative: Catestatinmentioning

confidence: 99%

The Role of Catestatin in Preeclampsia

Bralewska,

Pietrucha,

Sakowicz

2024

IJMS

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“…In mammalian cells, hypoxia-induced HIF-1α activity reduces growth by suppressing the activity of the mammalian Target of Rapamycin (mTOR) 70,71,72,73,74 , a major regulator of anabolic metabolism 75 . It is of interest therefore that TOR signalling activity, as assayed by phosphorylated ribosomal protein S6 (pS6) immunoreactivity, progressively decreases during the growth of L3 wing imaginal discs 76,77 , an observation that we confirmed by Western blot analysis (Extended Data Fig.…”

Section: Sima/hif-1α Dampens Tor Signalling Through Activation Of Scy...mentioning

confidence: 99%

Growth-induced physiological hypoxia correlates with growth deceleration during normal development

Zhao,

Alexandre,

Kelly

et al. 2024

Preprint

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Growth deceleration is a universal feature of growth during development: most organs and tissues slow down their growth rate much before growth termination. Using transcriptomics analysis, we show that during their two-day period of growth deceleration, wing imaginal discs ofDrosophilaundergo a progressive metabolic shift away from oxidative phosphorylation and towards glycolysis. We then develop an ultra-sensitive reporter HIF-1α activity, which reveals that imaginal discs become increasingly hypoxic during development in normoxic conditions, suggesting that limiting oxygen supply could underlie growth deceleration. Growth is energetically expensive and thus expected to contribute, indirectly, to oxygen consumption. Indeed, excess TOR signalling, a key stimulator of growth, triggers hypoxia locally and systemically, highlighting the need to rein in growth when oxygen becomes limiting. This is achieved by a negative feedback loop whereby the classic TOR-inhibitory function of HIF-1α is deployed in response to developmental hypoxia. The absence of Sima/HIF-1α leads to cellular stress, which is alleviated by reduced TOR signalling. Conversely, a small increase in oxygen supply reduces the stress induced by excess TOR activity. We conclude that mild hypoxia is a normal feature of organ development and that Sima/HIF-1α prevents growth-induced oxygen demand from exceeding supply.

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HIF-1α regulates mTOR signaling pathway during salivary gland development

Cited by 2 publications

References 25 publications

The Role of Catestatin in Preeclampsia

The Role of Catestatin in Preeclampsia

Growth-induced physiological hypoxia correlates with growth deceleration during normal development

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