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An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
Published on: April 17, 2013
Interrelationship between insulin-like growth factor I-induced activation of the Na+/H(+)-antiporter and
N Takasu1, I Komiya, Y Nagasawa
1Department of Gerontology, Endocrinology and Metabolism, School of Medicine, Shinshu University, Nagano-ken, Japan.
Insights
Insulin-like growth factor I (IGF-I) increases intracellular pH (pHi) and calcium in thyroid cells by activating the Na+/H+-antiporter. This pH shift optimizes the calcium response, a key biological function of IGF-I.
Area of Science:
- Cellular Biology
- Endocrinology
Background:
- Insulin-like growth factor I (IGF-I) plays a role in cellular processes.
- Intracellular pH (pHi) and calcium levels ([Ca2+]i) are critical for cell function.
Purpose of the Study:
- To investigate the role of the Na+/H+-antiporter in IGF-I-induced changes in pHi and [Ca2+]i in porcine thyroid cells.
- To elucidate the relationship between pHi and the [Ca2+]i response to IGF-I.
Main Methods:
- Cultured porcine thyroid cells were treated with IGF-I.
- The Na+/H+-antiporter was inhibited using dimethylamiloride or by reducing external Na+ concentrations.
- Changes in pHi and [Ca2+]i were measured.
Main Results:
- IGF-I significantly increased both pHi and [Ca2+]i in thyroid cells.
- Inhibition of the Na+/H+-antiporter attenuated the IGF-I-induced increases in pHi and [Ca2+]i.
- The [Ca2+]i response to IGF-I was found to be dependent on the resulting pHi.
- IGF-I activates the Na+/H+-antiporter, leading to cellular alkalinization.
Conclusions:
- IGF-I activates the Na+/H+-antiporter, increasing pHi in porcine thyroid cells.
- The observed increase in pHi facilitates the calcium response to IGF-I by optimizing the intracellular Ca2+-mobilizing system.
- Activation of the Na+/H+-antiporter by IGF-I is crucial for modulating intracellular calcium levels.
Abstract:
Insulin-like growth factor I (IGF-I) increased cytoplamic pH (pHi) and cytoplasmic Ca2+ [( Ca2+]i) in cultured porcine thyroid cells. Inhibition of the Na+/H(+)-antiporter by dimethylamiloride or a reduction of external Na(+)-concentrations attenuates the increases in pHi and [Ca2+]i. The [Ca2+]i response to IGF-I is a pHi-dependent process. IGF-I activates Na+/H(+)-antiporter and alkalinizes thyroid cells. The resulting increase in pHi facilitates the [Ca2+]i response by adjusting the pHi closer to the pHi-optimum of the intracellular Ca(2+)-mobilizing system. One of the biological functions of IGF-I-induced activation of the Na+/H(+)-antiporter is to shift the pHi to an optimal value for the [Ca2+]i response.
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