Fig 1: Mitochondrial cristae disruption and hydrolyzed JP2 nuclear translocation in myocardium of db/db mice. (A) Electron micrographs showed the decreased areas of cristae organization and density of mitochondria (M) in db/db mice compared with controls. Scale bar: 500 nm and 200 nm. (B) Representative images of echocardiography. Both left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) decreased. *P < 0.05, n=9 (BKS mice), n=7 (db/db mice). *P < 0.05, **P < 0.01. (C) The abundance and distribution of JP2 (red) changed in cardiomyocytes (green, cTnT) of T2D heart. The colocalization of JP2NT (red) with nuclei (blue, DAPI) appear in cardiomyocytes of T2D heart (arrow: nuclear JP2NT). (D) In the case of cardiac mitochondrial ultrastructure lesions, and cardiac dysfunction in T2D hearts, the hydrolyzed product JP2NT import into the nucleus of myocardium. Scale bar: 50 μm and 15 μm (left panel). Ratio of JP2NT existed in nuclei were showed in dot chart (right panel) (n=8~11, 4 random fields for each sample).
Fig 2: Increased transcription of Capns1 in the hearts of db/db mice. (A) Cardiac Capns1 transcription enhanced in db/db mice (16-weeks-old). (B) The transcription levels of substrates Jp2, Tnni3, and Mybpc3 in cardiac calpain/CAPNS1 pathway were not reduced (n=4, each sample was repeated three times). (C) Representative blotting showing JP2 protein decreased in expression in T2D hearts (n=3, each sample was repeated three times, #3 and #17 were original lab codes of animals). *P < 0.05.
Fig 3: ∣ Hypothesis contributing to crucial gene and key functions in T2D hearts with and without SARS-CoV-2 infection. Capns1/CAPNS1 is the unique gene shared by molecular function module and cellular components module of overlapped DEGs, and involved in catalyzing JP2 hydrolysis, T2D hearts should possess intrinsic CAPNS1-dependent self-protective mechanism. The autopsy heart specimens of T2D patients display attenuated transcription of CAPNS1 in the case of SARS-CoV-2 infection. Attenuated cardiac CAPNS1 transcription in T2D patients who succumbed to SARS-CoV-2 infection must decrease in the ability to hydrolyze JP2 and weaken self-protective mechanism, thereby leading to adverse prognostics.
Supplier Page from Abcam for Anti-JP-2 antibody