Visinin-Like Protein-3 Modulates the Interaction Between Cytochrome b 5 and NADH-Cytochrome b 5 Reductase in a Ca2+-Dependent Manner

Cell Biochem Biophys. 2016 Dec;74(4):449-457. doi: 10.1007/s12013-016-0753-6. Epub 2016 Jul 2.

Abstract

Visinin-like proteins (VILIPs) belong to the calcium sensor protein family. VILIP-1 has been examined as a cerebrospinal fluid biomarker and as a potential indicator for cognitive decline in Alzheimer's disease (AD). However, little is known about VILIP-3 protein biochemistry. We performed co-immunoprecipitation experiments to examine whether VILIP-3 can interact with reduced nicotine adenine dinucleotide (NADH)-cytochrome b 5 reductase. We also evaluated the specificity of cytochrome b 5 within the visinin-like protein subfamily and identified cytochrome P450 isoforms in the brain. In this study, we show that cytochrome b 5 has an affinity for hippocalcin, neurocalcin-δ, and VILIP-3, but not visinin-like protein-1. VILIP-3 was also shown to interact with NADH-cytochrome b 5 reductase in a Ca2+-dependent manner. These results suggest that VILIP-3, hippocalcin, and neurocalcin-δ provide a Ca2+-dependent modulation to the NADH-dependent microsomal electron transport. The results also suggest that future therapeutic strategies that target calcium-signaling pathways and VILIPs may be of value.

Keywords: Calcium; Calcium sensor; Electron transport; Mitochondria; Molecular; Nerve.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / metabolism
  • Calcium / chemistry
  • Calcium / metabolism
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cytochrome P-450 CYP4A / metabolism
  • Cytochrome-B(5) Reductase / chemistry
  • Cytochrome-B(5) Reductase / metabolism*
  • Cytochromes b5 / chemistry
  • Cytochromes b5 / metabolism*
  • HEK293 Cells
  • Hippocalcin / chemistry
  • Hippocalcin / metabolism
  • Humans
  • Immunoprecipitation
  • Ions / chemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurocalcin / chemistry
  • Neurocalcin / metabolism
  • Plasmids / genetics
  • Plasmids / metabolism
  • Protein Binding
  • Sequence Alignment

Substances

  • Calcium-Binding Proteins
  • Ions
  • Nerve Tissue Proteins
  • Neurocalcin
  • VILIP-3 protein, mouse
  • Hippocalcin
  • Cytochromes b5
  • Cytochrome P-450 CYP4A
  • Cytochrome-B(5) Reductase
  • Calcium