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Protein kinase C in mouse kidney: effect of the Hyp mutation and phosphate deprivation
1Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
Abstract:
To test whether protein kinase C plays a role in the regulation of renal brush border membrane phosphate transport and mitochondrial vitamin D metabolism, we examined the activity, distribution and endogenous substrates of protein kinase C in renal subcellular fractions derived from two mouse models exhibiting perturbations in both renal functions. The X-linked Hyp mouse is characterized by reduced phosphate transport and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) synthesis relative to normal, whereas the phosphate-deprived mouse exhibits elevated phosphate transport and vitamin D hormone synthesis. Protein kinase C activity was higher in renal cytosol of Hyp mice, when compared to normal littermates (358 +/- 11 vs. 244 +/- 31 pmol 32P/mg prot/min, P less than 0.02), whereas genotype differences in brush border membrane and mitochondrial kinase were not apparent. Phosphate deprivation of normal mice elicited a 50% reduction in brush border membrane protein kinase C (from 819 +/- 56 to 460 +/- 48 pmol 32P/mg prot/min, P less than 0.03), an increase in mitochondrial kinase (from 57 +/- 7 to 87 +/- 10 pmol 32P/mg prot/min, P less than 0.03), and no change in cytosolic kinase activity. Phosphate deprivation of Hyp mice led to an increase in mitochondrial protein kinase C (from 72 +/- 7 to 98 +/- 9 pmol 32P/mg prot/min, P less than 0.03) and no change in either brush border membrane or cytosolic kinase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Protein kinase C activity is altered in mouse models with kidney disorders affecting phosphate transport and vitamin D metabolism. These findings suggest protein kinase C
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- Renal brush border membrane phosphate transport and vitamin D metabolism are crucial for kidney function.
- Protein kinase C (PKC) is a family of enzymes involved in various cellular processes, including signal transduction.
- Dysregulation of these renal functions is observed in conditions like X-linked Hyp mice and phosphate-deprived states.
Purpose of the Study:
- To investigate the role of protein kinase C (PKC) in regulating renal phosphate transport and vitamin D metabolism.
- To examine PKC activity and distribution in mouse models with altered renal functions.
Main Methods:
- Analysis of protein kinase C activity in renal subcellular fractions (cytosol, brush border membrane, mitochondria).
- Comparison of PKC activity in X-linked Hyp mice and phosphate-deprived mice versus normal littermates.
- Measurement of PKC endogenous substrates and distribution.
Main Results:
- Protein kinase C activity was elevated in the renal cytosol of Hyp mice compared to normal controls.
- Phosphate deprivation reduced brush border membrane PKC activity in normal mice but increased mitochondrial PKC activity.
- Phosphate deprivation also increased mitochondrial PKC activity in Hyp mice.
Conclusions:
- Protein kinase C activity is modulated by phosphate transport and vitamin D metabolism status in the kidney.
- PKC may play a regulatory role in renal phosphate handling and vitamin D synthesis.
- Further research is needed to elucidate the specific mechanisms involved.