54
These new AMPs are integrated in the concept that highlights the key role of the
adrenal medulla in the immunity (Sternberg 2006 ) as previously reported for adren-
aline and neuropeptide Y that regulate immunity systemically once released from
the adrenal medulla. Furthermore, the adrenal medulla contains and releases large
amounts of interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in
response to pro-inflammatory stimuli such as lipopolysaccharide (LPS), IL-1 alpha
and IL-1 beta. The discovery of the presence of Toll like receptors (TLRs) on the
adrenal cortex cells raises the interesting possibility that the adrenal gland might
have a direct role in the response to pathogens, activation of innate immune response
and clearing of infectious agents (Sternberg 2006 ). We have more particularly stud-
ied VS-I and CAT.
VS-I displays antimicrobial activity against (i) Gram-positive bacteria
(Micrococcus luteus and Bacillus megaterium) with a minimal inhibitory concentra-
tion (MIC) in the range 0.1–1 μM; (ii) filamentous fungi (Neurospora crassa,
Aspergillus fumigatus, Alternaria brassicola, Nectria haematococca, Fusarium cul-
morum, Fusarium oxysporum) with a MIC of 0.5–3 μM and (iii) yeast cells
(Saccharomyces cerevisiae, Candida albicans) with a MIC of 2 μM (Lugardon et al.
2000 ). VS-I possesses structural features specific for antimicrobial peptides, such as
a global positive charge (+3), an equilibrated number of polar and hydrophobic resi-
dues (20:23) and the presence of a helical region CGA40-66 characterized to be a
calmodulin-binding sequence (Lugardon et al. 2001 ; Yoo 1992 ; Zhang et al. 2009b)
(Fig. 4a). The loss of the antibacterial activity of CGA7-57 suggests that the N- and
C-terminal sequences are essential and CGA7-57 is less efficient than VS-I against
fungi (Lugardon et al. 2000 ). Besides, the disulfide bridge is essential for the anti-
bacterial, but not the antifungal property. Altogether, these data suggest that antibac-
terial and antifungal activities of VS-I have different structural requirements
(Lugardon et al. 2000 ). Interestingly, two helix-helix dimerization motifs important
for the interaction with membranes such as LXXXXXXL, present in dopamine
transporter sequences (Torres et al. 2003 ) are present in the bovine and human VS-I
PeptideLocationSequence Net charge
CGA
VS-1 1-76 LPVNSPMNKGDTEVMKC*IVEVISDTLSKPSPMPVSKEC*FETLRGDERILSILRHQNLLKELQDLALQGAKERTHQQ +3
NCA4-40LPVNSPMNKGDTEVMKC*IVEVISDTLSKPSPMPVSKEC*FE- 1
CHR47-66 RILSILRHQNLLKELQDLAL +1,5
Chrom 173- 194 YPGPQAKEDSEGPSQGPASREK -1
CAT 344- 364 RSMRLSFRARGYGFRGPGLQL +5
CCA 418- 427 LEKVAHQLEE -2
ProChrom79- 431 HSSYEDELSEVLEK..... -37Fig. 3 Location, sequence and net charge of the antimicrobial peptides derived from CgA; C*
cysteine residues involved in disulfide bridges, Y phosphorylated residue, S O-glycosylated residue
(Helle et al. 2007 )
M.-H. Metz-Boutigue and F. Schneider