Intermediate-luminosity Type IIP SN 2021gmj: a low-energy explosion with signatures of circumstellar material

We present photometric, spectroscopic and polarimetric observations of the intermediate-luminosity Type IIP supernova (SN) 2021gmj from 1 to 386 days after the explosion. The peak absolute V-band magnitude of SN 2021gmj is -15.5 mag, which is fainter than that of normal Type IIP SNe. The spectral evolution of SN 2021gmj resembles that of other sub-luminous supernovae: the optical spectra show narrow P-Cygni profiles, indicating a low expansion velocity. We estimate the progenitor mass to be about 12 Msun from the nebular spectrum and the 56Ni mass to be about 0.02 Msun from the bolometric light curve. We also derive the explosion energy to be about 3 x 10^{50} erg by comparing numerical light curve models with the observed light curves. Polarization in the plateau phase is not very large, suggesting nearly spherical outer envelope. The early photometric observations capture the rapid rise of the light curve, which is likely due to the interaction with a circumstellar material (CSM). The broad emission feature formed by highly-ionized lines on top of a blue continuum in the earliest spectrum gives further indication of the CSM at the vicinity of the progenitor. Our work suggests that a relatively low-mass progenitor of an intermediate-luminosity Type IIP SN can also experience an enhanced mass loss just before the explosion, as suggested for normal Type IIP SNe.Comment: 18 pages, 16 figures, resubmitted to MNRAS after addressing referee comment

Gemcitabine Induces Poly (ADP-Ribose) Polymerase-1 (PARP-1) Degradation through Autophagy in Pancreatic Cancer

<div><p>Poly (ADP-ribose) polymerase-1 (PARP-1) and autophagy play increasingly important roles in DNA damage repair and cell death. Gemcitabine (GEM) remains the first-line chemotherapeutic drug for pancreatic cancer (PC). However, little is known about the relationship between PARP-1 expression and autophagy in response to GEM. Here we demonstrate that GEM induces DNA-damage response and degradation of mono-ADP ribosylated PARP-1 through the autophagy pathway in PC cells, which is rescued by inhibiting autophagy. Hypoxia and serum starvation inhibit autophagic activity due to abrogated GEM-induced mono-ADP-ribosylated PARP-1 degradation. Activation of extracellular regulated protein kinases (ERK) induced by serum starvation shows differences in intracellular localization as well as modulation of autophagy and PARP-1 degradation in GEM-sensitive KLM1 and -resistant KLM1-R cells. Our study has revealed a novel role of autophagy in PARP-1 degradation in response to GEM, and the different impacts of MEK/ERK signaling pathway on autophagy between GEM-sensitive and -resistant PC cells.</p></div

Serum starvation induces activation and different localization of extracellular ERK between KLM1 and KLM1-R cells.

<p>(A) KLM1 and KLM1-R cells were cultured in medium with or without FBS or exposed to 10 μg/mL of GEM for 24 h. Cell lysates were resolved by SDS-PAGE and probed with specific antibodies against p-ERK and ERK. (B) and (C) The indicated cells were stained with specific antibodies against p-ERK, Hsp27 and LC3A/B after cells were cultured in medium with or without FBS for 24 h. DAPI: blue and p-ERK: red in (B) and LC3A/B: green and Hsp27: red in (C). Scale bar, 20 μm.</p

Hypoxia suppresses autophagy and GEM-induced PARP-1 degradation.

<p>(A) KLM1 and KLM1-R cells were cultured in normal conditions or 1% O₂ hypoxia for 24 hours, and then cell lysates were resolved by SDS-PAGE and probed with specific antibodies. (B) The indicated cells were cultured in normal conditions or 1% O₂ hypoxia together with 10 μg/mL of GEM for 24 hours. Cell lysates were resolved by SDS-PAGE and probed with specific antibodies. An arrow head indicates the mono-ADP ribosylated form of PARP-1. Arrows indicate the position area of cleaved caspase-3. The expression of PARP-1 was confirmed repeatedly by a distinct PARP-1 antibody described in Materials.</p

Serum starvation suppresses GEM-induced PARP-1 degradation through inhibition of autophagy via the ERK signaling pathway.

<p>(A) KLM1 and KLM1-R cells were exposed to 10 μg/mL of GEM in the presence or absence of 20 μM of U0126 for the indicated time courses. Cell lysates were resolved by SDS-PAGE and probed with specific antibodies against p-ERK and LC3A/B. (B) and (C) KLM1 and KLM1-R cells were cultured in the medium with or without FBS and meanwhile exposed to either or both GEM and U0126 at the indicated concentration. Cell lysates were resolved by SDS-PAGE and probed with specific antibodies. The arrow head indicates the mono-ADP ribosylated form of PARP-1. Arrows indicate the position area of cleaved caspase-3. The expression of PARP-1 was confirmed repeatedly by a distinct PARP-1 antibody described in Materials.</p