Parathormone sensitivity and responses to protein kinases in subclones of opossum kidney cells

Douglas M Silverstein1, Adrian Spitzer, Mario Barac-Nieto

  • 1Division of Nephrology, Department of Pediatrics, Health Sciences Center, Louisiana State University, New Orleans, 70118, USA. dsilve@lsuhsc.edu

Insights

Parathyroid hormone (PTH) and protein kinase (PK) effectors differentially regulate sodium-dependent phosphate (Na-Pi) transport in opossum kidney (OK) cells. This study reveals functional heterogeneity in OK cell responses to these regulators.

Area of Science:

  • Nephrology
  • Cell Physiology
  • Molecular Biology

Background:

  • Parathyroid hormone (PTH) is known to inhibit renal sodium-dependent phosphate (Na-Pi) cotransport.
  • This inhibition involves protein kinases A (PKA) and C (PKC), and 20-hydroxyeicosatetraneoic acid (20-HETE).
  • Variability in reported effects suggests functional heterogeneity among opossum kidney (OK) cell subclones.

Purpose of the Study:

  • To investigate the effect of PTH and PK effectors on Na-Pi transport in distinct sets of OK cells.
  • To explore the functional heterogeneity of OK cells in response to Na-Pi transport regulators.

Main Methods:

  • Two separate groups of OK cells, derived from the same stock, were used.
  • Cells were treated with PTH, 20-HETE, TPA (a PKC activator), and staurosporine (a PKC inhibitor).
  • Sodium- and phosphate (Na-(32)Pi) transport was measured using radiolabeled phosphate uptake.

Main Results:

  • Group 1 OK cells showed inhibition of Na-Pi transport by 20-HETE, PTH, TPA, and Br-cAMP.
  • Group 2 OK cells exhibited increased Na-Pi transport with 20-HETE and TPA, while PTH had no significant effect.
  • PKC inhibition with staurosporine increased Na-Pi transport in Group 1, but slightly decreased it in Group 2, with simultaneous 20-HETE restoring baseline in both.

Conclusions:

  • OK cell subclones demonstrate markedly different responses to regulators of Na-Pi cotransport.
  • Functional heterogeneity exists within OK cell populations, impacting their response to hormonal and signaling pathways.
  • These findings highlight the importance of considering cell subclone variability in renal phosphate transport studies.

Related Concept Videos

The Parathyroid Glands00:59

The Parathyroid Glands

The two pairs of parathyroid glands embedded within the posterior surface of the thyroid gland are restricted by a dense capsule around them. These glands comprise two distinct cell populations—parathyroid oxyphil and parathyroid principal cells- pivotal in calcium homeostasis.
Oxyphil cells, whose functions remain elusive, emerge during late puberty, adding a layer of complexity to the parathyroid gland's intricacies. In contrast, principal parathyroid cells undertake a vital role by producing...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Hormones and Bone Tissue01:17

Hormones and Bone Tissue

The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...