2019 Targeting Trends Review

Toledo C, Andrade DC, Del Rio R (2019) Brainstem pre-sympathetic neurons contribute to irregular breathing patterns in volume overload heart failure. FASEB J 33(1):lb630. Experimental Biology 2019 Meeting Abstracts doi: 10.1096/fasebj.2019.33.1_supplement.lb630

Objective: To investigate the contribution of RVLM-C1 neurons on breathing disorders in chronic heart failure (CHF).

Summary: RVLM-C1 neurons play a critical role in the maintenance of altered breathing patterns in CHF rats and highlighted their contribution to the worsening of cardiac function during central chemoreflex activation. DBH-SAP treatment decreased active expiration in CHF rats and deleterious effects of central chemoreflex activation on diastolic cardiac function and cardiac autonomic control were blunted.

Usage: Stereotaxic bilateral injections of Anti-DBH-SAP (5 ng/150 nl).

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Manavella DD, Cacciottola L, Payen VL, Amorim CA, Donnez J, Dolmans MM (2019) Adipose tissue-derived stem cells boost vascularization in grafted ovarian tissue by growth factor secretion and differentiation into endothelial cell lineages. Mol Hum Reprod 25(4):184-193. doi: 10.1093/molehr/gaz008 PMID: 30824937

Usage: immunohistochemistry (1:2000)

Related Products: Fibroblast Growth Factor Rabbit Polyclonal, mammalian (Cat. #AB-07)

Sajjadi E, Seven YB, Simon AK, Zwick A, Satriotomo I, Mitchell GS (2019) Adenosine 2A receptor inhibition promotes neuroprotection following toxic insult to phrenic motor neurons. FASEB J 33(1):844.3. Experimental Biology 2019 Meeting Abstracts doi: 10.1096/fasebj.2019.33.1_supplement.844.3

Objective: The authors explored the role of A2A receptors in phrenic motor neuron cell death in vivo.

Summary: A2A receptors, which contribute to motor neuron death during toxic insults, are upregulated in spared phrenic motor neurons of CTB-SAP treated rats. This is an important finding since A2A receptor upregulation may accelerate motor neuron death in neurodegenerative diseases like ALS.

Usage: CTB-SAP selectively killed nearly all phrenic motor neurons within a week and caused diaphragm paralysis (p<0.01).

Related Products: CTB-SAP (Cat. #IT-14)

Krajewski-Hall SJ, Miranda Dos Santos F, McMullen NT, Blackmore EM, Rance NE (2019) Glutamatergic neurokinin 3 receptor neurons in the median preoptic nucleus modulate heat-defense pathways in female mice. Endocrinology 160(4):803-816. doi: 10.1210/en.2018-00934

Objective: To characterize the thermoregulatory role of MnPO NK3R neurons in female mice.

Summary: Study suggests that KNDy neurons modulate thermosensory pathways for heat defense indirectly via a subpopulation of glutamatergic MnPO neurons that express NK3R.

Usage: Mice were bilaterally injected with 10 ng NK3-SAP in 100 nL PBS (n = 14) or blank-SAP (n = 8) in the preoptic area adjacent to the MnPO.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Borkowski LF, Nichols NL (2019) A2A and 5‐HT receptors are differentially required for respiratory plasticity over the course of motor neuron loss in intrapleurally CTB-SAP treated rats. FASEB J 33(1):843.3. Experimental Biology 2019 Meeting Abstracts doi: 10.1096/fasebj.2019.33.1_supplement.843.3

Objective: To investigate the role of serotonin (5-HT) and adenosine 2A (A2A) receptors in respiratory plasticity.

Summary: A2A receptors are necessary for respiratory plasticity early (7d), but 5-HT receptors are required late (28d).

Usage: Bilateral, intrapleural injections of: 1) CTB-SAP (25 μg), or 2) un-conjugated CTB and SAP (control) in rats.

Related Products: CTB-SAP (Cat. #IT-14)

Souza G, Stornetta R, Stornetta D, Abbott S, Guyenet P (2019) Contribution of retrotrapezoid nucleus and carotid bodies to asphyxia‐induced arousal in rats. FASEB J 33(1):733.6. Experimental Biology 2019 Meeting Abstracts doi: 10.1096/fasebj.2019.33.1_supplement.733.6

Objective: To determine whether the retrotrapezoid nucleus (RTN) is implicated in CO2-induced arousal.

Summary: The authors confirm the importance of the CBs to hypoxia-induced arousal and demonstrate that arousal to hypercapnia is selectively reduced after RTN lesion.

Usage: RTN was nearly completely destroyed with microinjections of SSP-SAP (2.4 ng).

Related Products: SSP-SAP (Cat. #IT-11)

Im E-J, Lee C-H, Moon P-G, Rangaswamy GG, Lee B, Lee JM, Lee J-C, Jee J-G, Bae J-S, Kwon T-K, Kang K-W, Jeong M-S, Lee J-E, Jung H-S, Ro H-J, Jun S, Kang W, Seo S-Y, Cho Y-E, Song B-J, Baek M-C (2019) Sulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A. Nature Commun 10(1):1387. doi: 10.1038/s41467-019-09387-4 PMID: 30918259

Objective: To identify a direct protein target of SFX in cancer cells.

Summary: Using data from the BindingDB, SEA identified four proteins as target candidates, which are: endothelin receptor type A, kynurenine 3-monooxygenase, carbonic anhydrase 13, and angiotensin II type 1a receptor.

Usage: Western blot (1:1000).

Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP)

Gulino R, Vicario N, Giunta MAS, Spoto G, Calabrese G, Vecchio M, Gulisano M, Leanza G, Parenti R (2019) Neuromuscular plasticity in a mouse neurotoxic model of spinal motoneuronal loss. Int J Mol Sci 20(6):1500. doi: 10.3390/ijms20061500

Objective: To use a neurotoxic model of spinal motoneuron depletion, induced by injection of CTB-SAP, to investigate the possible occurrence of compensatory changes in both the muscle and spinal cord.

Summary: Plastic changes in surviving motoneurons produce a functional restoration probably similar to the compensatory changes occurring in disease. These changes could be driven by glutamatergic signaling; astrocytes contacting surviving motoneurons may support this process.

Usage: Mice received 2 injections of CTB-SAP (3 mcg CTB-Sap in 2 mcL PBS) into the medial and lateral left gastrocnemius muscle.

Related Products: CTB-SAP (Cat. #IT-14)

Eidson LN, Murphy AZ (2019) Inflammatory mediators of opioid tolerance: Implications for dependency and addiction. Peptides 115:51-58. doi: 10.1016/j.peptides.2019.01.003

Objective: To determine what mediates opioid tolerance and alterations in glutamate homeostasis.

Summary: Site-specific lesions of PAG MOR-containing neurons using Dermorphin-SAP significantly reduce the antinociceptive effects of systemic morphine suggesting that PAG MOR is critical for morphine action.

Usage: Rats were injected with 3 pmol of Dermorphin-SAP (Cat. #IT-12) into the PAG. Blank-SAP (Cat. #IT-21) was used as a control.

See: Loyd DR et al. Sex differences in micro-opioid receptor expression in the rat midbrain periaqueductal gray are essential for eliciting sex differences in morphine analgesia. J Neurosci 28:14007-14017, 2008.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21)

Ji J, Tao P, He L (2019) Kangxianling decoction prevents renal fibrosis in rats with 5/6 nephrectomy and inhibits Ang II-induced ECM production in glomerular mesangial cells. J Pharmacol Sci 139(4):367-372. doi: 10.1016/j.jphs.2019.03.003 PMID: 30929858

Objective: To investigate effects of Kangxianling decoction on renal fibrosis in a rat model of 5/6 Nephrectomy (5/6 N) in vivo and in angiotensin II (Ang II)-treated rat glomerular mesangial cells (HBZY-1) in vitro.

Summary: Kangxianling decoction could reduce renal fibrosis, accompanied by inhibiting the production of ECM proteins and JNK, along with downregulation of TGF-β, Ang II.

Usage: Western blot analysis (1:100).

Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP)