# CALCIUM AND CELL GROWTH

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 1991 · $179,325

## Abstract

Platelet-Derived Growth Factor (PDGF) through its biological activities of
mitogenesis, chemotaxis, and vasoconstriction, has been implicated in the
disease processes of cancer, atherosclerosis, and hypertension.  PDGF
elicits these activities through the existence of distinct PDGF isoforms
(AB heterodimer and AA and BB homodimers) and receptors.  However, the
mechanism(s) by which PDGF binding to its receptors is transduced into
biological activity is not clear.  We have obtained preliminary data
supporting a role for alterations in cytosolic free calcium ([Ca++]i) in
PDGF-stimulated mitogenesis.  The overall goal of this proposal is to test
the hypothesis that early alterations in [Ca++]i which occur within seconds
to minutes after PDGF binding, are necessary for PDGF stimulated
mitogenesis, and that the amplitude and kinetics of the [Ca++]i response
are modulated by other PDGF-induced alterations in cellular functions.
Therefore our specific aims are:  1) Determination of the role of early
PDGF-isoform-induced alterations in [Ca++]i in PDGF-stimulated mitogenic
activity; and 2) Determination of the cellular mechanisms of modulation of
PDGF-isoform-induced alterations in [Ca++]i.  Using Multiparameter
Digitized Video Microscopy (MDVM) which allows the real time observation of
a number of cellular functions at the level of a single intact living cell,
we will monitor [Ca++]i and DNA synthesis in the same vascular smooth
muscle cell (VSMC) following treatment with PDGF isoforms.  These induced
alterations in [Ca++]i by manipulation of the extracellular ionic
environment or pharmacologic antagonists, through the use of Ca++
ionophores, caged Ca++ or caged Ca++ buffer, and by microinjection of
BAPTA-conjugated dextran.  We will also monitor, in the same VSMC, [Ca++]i
and plasma membrane potential (VM), to determine whether PDGF-isoform-
induced alterations in [Ca++]i are modulated by VM, and [Ca++]i can also be
modulated by pHi.  The role of inositol trisphosphate (IP3), Ca++ itself
and activated Protein Kinase C (PKC) in PDGF-isoform-induced alterations in
[Ca++]i will be examined using caged IP3, caged Ca++ and caged
diacylglycerol, in conjunction with the Ca++-sensitive fluorophore fluo-3.
The studies proposed here will provide substantial new information
regarding the role of calcium in cell growth, the importance of early
changes in [Ca++]i in PDGF-stimulated mitogenesis, and whether alterations
in other cellular functions caused by PDGF (e.g. VM, pHi, IP3 and PKC
activation), via modulation of PDGF-induced alterations in [Ca++]i can
influence PDGF mitogenic activity.  Such information will be of importance
as it may aid in the development of therapeutic modalities to treat PDGF-
dependent disease conditions.

## Key facts

- **NIH application ID:** 3122060
- **Project number:** 1R01AG010104-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **SAM.gov UEI:** D3LHU66KBLD5
- **Principal Investigator:** BRIAN A. HERMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $179,325
- **Award type:** 1
- **Project period:** 1991-06-15 → 1994-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122060

## Citation

> US National Institutes of Health, RePORTER application 3122060, CALCIUM AND CELL GROWTH (1R01AG010104-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122060. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*